interleukin-8 and Hypertension

Hypertension is a long-term medical condition in which the blood pressure is gradually elevated. In this project, the effects of olive leaf extract (OLE) were evaluated on metabolic response, liver and kidney functions and also biomarkers of inflammation in hypertensive patients.. In this randomized double-blind placebo controlled clinical trial, 60 hypertensive patients, aged 30-60 years old had participated. Patients were randomly assigned into two groups to receive either OLE or placebo tablets for 12 weeks. At the beginning and end of the intervention, metabolic parameters and biomarkers of liver, kidney and inflammation were measured in sera of the participants using available laboratory methods.. Compared with the placebo, changes in parameters associated with glucose metabolism were not statistically significant (p>0.05). The OLE tablets did not have significant effect on liver enzymes, total protein, albumin, urea and creatinine (p>0.05), but significantly decreased interleukin-6, interleukin-8 and tumor necrosis factor alpha as inflammatory biomarkers (p<0.05) in OLE group compared to the placebo group.. The results concluded that inflammation as a major cause of hypertension was significantly decreased in patients using OLE tablets.

Topics: Adult; Aged; Albumins; Biomarkers; Body Mass Index; Body Weight; Creatinine; Double-Blind Method; Female; Humans; Hypertension; Inflammation; Interleukin-6; Interleukin-8; Kidney; Liver; Male; Middle Aged; Olea; Plant Extracts; Plant Leaves; Tumor Necrosis Factor-alpha; Urea

High Na and low K intakes have adverse effects on blood pressure, which increases the risk for CVD. The role of endothelial dysfunction and inflammation in this pathophysiological process is not yet clear. In a randomised placebo-controlled cross-over study in untreated (pre)hypertensives, we examined the effects of Na and K supplementation on endothelial function and inflammation. During the study period, subjects were provided with a diet that contained 2·4 g/d of Na and 2·3 g/d of K for a 10 460 kJ (2500 kcal) intake. After 1-week run-in, subjects received capsules with supplemental Na (3·0 g/d), supplemental K (2·8 g/d) or placebo, for 4 weeks each, in random order. After each intervention, circulating biomarkers of endothelial function and inflammation were measured. Brachial artery flow-mediated dilation (FMD) and skin microvascular vasomotion were assessed in sub-groups of twenty-two to twenty-four subjects. Of thirty-seven randomised subjects, thirty-six completed the study. Following Na supplementation, serum endothelin-1 was increased by 0·24 pg/ml (95 % CI 0·03, 0·45), but no change was seen in other endothelial or inflammatory biomarkers. FMD and microvascular vasomotion were unaffected by Na supplementation. K supplementation reduced IL-8 levels by 0·28 pg/ml (95 % CI 0·03, 0·53), without affecting other circulating biomarkers. FMD was 1·16 % (95% CI 0·37, 1·96) higher after K supplementation than after placebo. Microvascular vasomotion was unaffected. In conclusion, a 4-week increase in Na intake increased endothelin-1, but had no effect on other endothelial or inflammatory markers. Increased K intake had a beneficial effect on FMD and possibly IL-8, without affecting other circulating endothelial or inflammatory biomarkers.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Brachial Artery; Cross-Over Studies; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypertension; Interleukin-8; Male; Middle Aged; Potassium, Dietary; Regional Blood Flow; Sodium, Dietary; Vasodilation

Hypertension is known to be one of the main risk factors for cardiovascular disease.. To evaluate the safety and efficacy of a fixed olmesartan/amlodipine (Olme/Amlo) combination in improving blood pressure control, lipid profile, insulin sensitivity and some inflammatory and insulin resistance markers. Two hundred and seventy-six hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or a single pill containing an Olme/Amlo combination 20/5 mg for 12 months. We evaluated after 6 and 12 months: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, vaspin, visfatin, interleukins 8 and 10 (IL-8 and IL-10, respectively). Patients also underwent an euglycemic, hyperinsulinemic clamp.. Olme/Amlo combination was more effective in decreasing SBP, and DPB compared to single monotherapies after 12 months. Olme/Amlo combination, but not amlodipine, decreased FPG after 12 months. FPI and HOMA index were decreased, and M value increased by Olme/Amlo combination compared to olmesartan monotherapy, and to amlodipine monotherapy. Olme/Amlo significantly decreased IL-8 and IL-10 better than each monotherapy.. Olme/Amlo single pill combination can be a safe and effective option to reduce blood pressure, improve insulin sensitivity and decrease inflammatory markers.

Topics: Adipokines; Amlodipine; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypertension; Imidazoles; Inflammation; Insulin; Insulin Resistance; Interleukin-10; Interleukin-8; Lipids; Male; Middle Aged; Tetrazoles

To explore the ATF2 expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients.. Preeclampsia is a severe pregnancy-related hypertension disorder and refers to hypertension.. This study was designed to explore the activating transcription factor 2 (ATF2) expression of preeclampsia patients and investigate whether the level of ATF2 expression impacted the low-dose aspirin treatment of preeclampsia patients.. Firstly, we collected the plasma of normal and preeclampsia pregnancies and quantified the expressions of ATF2 by ELISA. Then we quantified the expression of the three downstream target genes of ATF2 (IL-8, IL-6 and MMP-2). Finally, we collected and quantified the interventional and observational group plasma. All data were compared by t-test (p<0.05).. ATF2 and its target genes (IL-6, IL-8 and MMP-2) were upregulated in preeclampsia patients. In addition, ATF2 and its target genes were downregulated in the interventional group (LDA-treated group).. Our results indicated that LDA could inhibit ATF2 expression in preeclampsia. It suggests that ATF2 may be a potential target of LDA in the prevention of preeclampsia.

Topics: Activating Transcription Factor 2; Aspirin; Female; Humans; Hypertension; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 2; Pre-Eclampsia; Pregnancy

To investigate the clinical value of platelet and inflammatory factor activation in vascular endothelial injury in hypertension.. A total of 120 hypertension patients diagnosed in our hospital from December 2019 to June 2021 were enrolled as study objects (Hypertension group); besides, another cohort of 60 healthy people undergoing physical examination at the same period were recruited as the controls (Control group). Next, the baseline clinical characteristics of subjects in the two groups were recorded and compared. Specifically, a hematology analyzer was adopt for detecting the mean platelet volume (MPV), platelet distribution width (PDW) and platelet hematocrit (PCT); ELISA for the level of IL-6, IL-8 and TNF-α; PHILIPS EPIQ 7 C (a device assessing endothelial vasodilator function in a non-invasive fashion) for reactive hyperemia index (RHI); univariate and multivariate regression analysis for risk factors triggering endothelial dysfunction; and Spearman correlation analysis for the correlation of platelet activation indicators and inflammatory factor level with vascular endothelial function.. Compared with the Control group, the patients in the Hypertension group exhibited higher levels of MPV, PDW, PCT, inflammatory factors (IL-6, IL-8 and TNF-α) and lower RHI. Moreover, Spearman correlation analysis showed a significant negative correlation of MPV, PDW, PCT, IL-6, IL-8 and TNF-α level with RHI level. In addition, univariate and multivariate regression analysis presented that MPV, PCT, IL-8 and TNF-α were risk factors for vascular endothelial dysfunction.. The activation of platelet and inflammatory factor is closely related to vascular endothelial function injury in patients with hypertension. To be specifically, platelet and inflammatory factor activation can effectively reflect the vascular endothelial function injury in patients with hypertension and has high clinical value.

Topics: Blood Platelets; Essential Hypertension; Humans; Hypertension; Interleukin-6; Interleukin-8; Mean Platelet Volume; Platelet Activation; Platelet Count; Tumor Necrosis Factor-alpha

Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kβ (NF-kβ), interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kβ (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1β (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kβ. These results contribute to better characterizing cardiovascular risk in hypertensives.

Topics: Blood Glucose; C-Reactive Protein; Creatinine; Humans; Hyperglycemia; Hypertension; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Lipids; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

The aim: To determine the role of selenium and Selenoprotein P in the intensification of inflammation processes, deviations of the functional state of the liver and the progression of changes in its parenchyma in patients with NAFLD and hypertension.. Material and methods: Study included 100 gender and age matched NAFLD patients: 49 (67.3 % women) hypertensive (main group) and 51 (58.8 % women) non-hypertensive NAFLD patients. 20 individuals (55.0 % women) formed control group. Diagnosis of NAFLD and hypertension was made according to respective guidelines. All patients underwent measurement of liver transferases, selenium, Selenoprotein P, IL-8 and IL-10.. Results: In both study groups, ALT and AST levels were significantly predominant in patients with steatohepatitis than steatosis. Increase in IL-8 and IL-10 was found in main study groups but not in subgroup analysis. In hypertensive NAFLD patients with steatosis, ALT correlated with selenium and Selenoprotein P. A direct correlation was between the de Ritis index and IL-8. Selenium correlated with IL-8 but not IL-10. Selenoprotein P correlated inversely with IL-8 and directly with IL-10.. Conclusions: Intensification of inflammation and depletion of antioxidant protection under presence of hypertension deepen redox violations in NAFLD patients. Such changes can be only partially compensated by anti-inflammatory and antioxidative activity. Selenium and Selenoprotein P are important substances in progression of NAFLD and should be assessed regarding diagnosis and treatment of NAFLD patients.

Topics: Antioxidants; Female; Humans; Hypertension; Inflammation; Interleukin-8; Male; Non-alcoholic Fatty Liver Disease; Selenium; Selenoprotein P

The article presents data on the state of cytokine regulation, indicators of endothelial damage when exposed to industrial vibration (general, local) and in combination with arterial hypertension.. To improve the quality of early diagnosis and prevention of vibration disease in an isolated course and its combination with arterial hypertension based on a study of the cytokine profile, biomarkers of endothelial dysfunction in this pathology.. A comprehensive survey of 84 patients with isolated vibration disease from the effects of local, general, first, second degree and 61 patients with a combined course of vibration disease from the effects of local, general second degree vibration and arterial hypertension, 30 people in the control group without contact with industrial vibration and found healthy by medical examination. The levels of pro-inflammatory (IL-1, IL-8, TNF-) and anti-inflammatory cytokines (IL-4), biomarkers of endothelial damage (EDN-1, TGF-1, VEGF-A, PDGF-BB, fibronectin, Willebrand factor) were determined using the enzyme immunoassay method.. The response of the immune system to the effects of industrial vibration is characterized by a cytokine imbalance an increase in the level of pro-inflammatory cytokines (IL-1, IL-8, TNF-) and a decrease in the level of anti-inflammatory cytokine (IL-4). With a combined course of vibratory disease and arterial hypertension, the cytokine imbalance is characterized by an even more significant increase in serum IL-1, IL-8, TNF- and a decrease in serum IL-4 concentration. Endothelial dysfunction with WB from the action of both local and general vibration in combination with hypertension is characterized by a significant increase in serum EDN-1, TGF-1, VEGF-A, PDGF-BB, fibronectin, Willebrand factor.. The study of the cytokine profile, biomarkers of damage to the vascular endothelium in this pathology will allow for the early diagnosis of vascular disorders and to optimize preventive measures for workers in vibration-hazardous industries.. Обоснование. В статье представлены данные о состоянии цитокиновой регуляции, показателях эндотелиального повреждения при воздействии промышленной вибрации (локальной ЛВ, общей ОВ) и при наличии коморбидного течения артериальной гипертензии (АГ). Цель. Улучшить качество ранней диагностики и профилактики ВБ при изолированном течении и ее сочетании с АГ на основании изучения цитокинового профиля, биомаркеров эндотелиальной дисфункции при данной патологии. Материалы и методы. Проведено комплексное обследование 84 пациентов с изолированной ВБ, связанной с воздействием ЛВ, ОВ 1, 2-й степени, и 61 пациента с сочетанным течением ВБ, связанной с воздействием ЛВ, ОВ 2-й степени и АГ, 30 человек контрольной группы, не имеющих контакта с промышленной вибрацией и признанных здоровыми по данным медицинского осмотра. Определены уровни провоспалительных (интерлейкина ИЛ-1, ИЛ-8, фактора некроза опухоли ФНО-) и противовоспалительных цитокинов (ИЛ-4), биомаркеров эндотелиального повреждения (эндотелина-1, трансформирующего фактора роста 1, фактора роста эндотелия А, тромбоцитарного фактора роста ВВ, фибронектина, фактора Виллебранда) с помощью иммуноферментного метода. Результаты. Реакция иммунной системы на воздействие производственной вибрации характеризуется цитокиновым дисбалансом повышением уровня провоспалительных цитокинов (ИЛ-1, ИЛ-8, ФНО-) и снижением уровня противовоспалительного цитокина (ИЛ-4). При сочетанном течении ВБ и АГ цитокиновый дисбаланс характеризуется еще более значимым повышением сывороточной концентрации ИЛ-1, ИЛ-8, ФНО- и снижением сывороточной концентрации ИЛ-4. Эндотелиальная дисфункция при ВБ, связанной с воздействием как ЛВ, так и ОВ, при наличии коморбидного течения АГ характеризуется достоверным повышением содержания в сыворотке крови эндотелина-1, трансформирующего фактора роста 1, фактора роста эндотелия А, тромбоцитарного фактора роста ВВ, фибронектина, фактора Виллебранда. Заключение. Изучение цитокинового профиля, биомаркеров повреждения сосудистого эндотелия при данной патологии позволит проводить раннюю диагностику сосудистых нарушений и оптимизировать профилактические мероприятия у работников виброопасных производств.

Topics: Anti-Inflammatory Agents; Becaplermin; Biomarkers; Cytokines; Fibronectins; Humans; Hypertension; Interleukin-1; Interleukin-4; Interleukin-8; Vascular Endothelial Growth Factor A; Vibration

To investigate the association between single nucleotide polymorphisms (SNPs) in endothelial nitric oxide synthase (eNOS) and interleukin-8 (IL-8) genes and risk of developing bevacizumab-related adverse events in metastatic breast cancer (mBC) patients.. mBC patients candidate to receive bevacizumab-based chemotherapy were enrolled in this pharmacogenetic study. eNOS c.-813C>T and c.894G>T, and IL-8 c.-251A>T were analyzed by real time PCR on genomic DNA extracted from peripheral blood. Univariate analysis was performed to test the association between each SNP and treatment-related toxicities.. Seventy-six mBC patients were enrolled in the present study. Patients carrying the homozygous variant eNOS c.-813TT genotype showed a statistically significant occurrence of any grade proteinuria when compared to CT or CC genotypes (p = 0.004). No significant association of proteinuria with IL-8 SNP or hypertension with selected eNOS and IL-8 SNPs was found.. These findings suggest an association between the eNOS c.-813C>T polymorphism and the development of proteinuria in mBC patients receiving a bevacizumab-based chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; Hypertension; Interleukin-8; Kaplan-Meier Estimate; Male; Middle Aged; Nitric Oxide Synthase Type III; Polymorphism, Single Nucleotide; Progression-Free Survival; Proteinuria

The impact of pregnancy hypertension in the offspring endothelia remains unknown. We evaluated the transcriptional expression of four genes that participate in the process of endothelial dysfunction using umbilical vein endothelial cell cultures (HUVEC) from healthy pregnant women (PW) and those with hypertensive disorders (HD). The cytochrome P450 1A1 (CYP1A1), gluthathione S-transferase subtype T1 (GSTT1), interleukin 6 (IL-6) and 8 (IL-8) mRNA and IL-6 protein levels were assessed. IL-6 and IL-8 transcripts were significantly reduced in HUVEC obtained from HD women. Our results suggest that a hypertensive environment in utero modifies the transcriptional expression of key inflammatory molecules in the newborn.

Topics: Adult; Case-Control Studies; Cytochrome P-450 CYP1A1; Endothelium, Vascular; Female; Glutathione Transferase; Human Umbilical Vein Endothelial Cells; Humans; Hypertension; Interleukin-6; Interleukin-8; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Transcription, Genetic; Umbilical Veins; Young Adult

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.

Topics: Adipocytes; Adipokines; Adiponectin; Animals; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Rats; RNA, Small Interfering; Sleep Apnea, Obstructive; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-β and TNF-α.. This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-β and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique.. With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-β and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-β were also increased in females in comparison to males in the group 4.. According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-β.

Topics: Antihypertensive Agents; Atorvastatin; Captopril; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Inflammation; Interleukin-6; Interleukin-8; Iran; Losartan; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Up-Regulation

Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults. This cross-sectional pilot study on obese adolescents was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for CVD.. The study included 75 obese subjects between 12 to 18 years of age, mean 14.5. Subjects answered a questionnaire regarding health, oral hygiene habits and sociodemographic factors. A clinical examination included Visible Plaque Index (VPI %), Gingival inflammation (BOP %) and the occurrence of pathological pockets exceeding 4 mm (PD ≥ 4 mm). Blood serum were collected and analyzed. The systolic and diastolic blood pressures were registered.. Adolescents with pathological periodontal pockets (PD ≥ 4 mm; n = 14) had significantly higher BOP >25% (P = 0.002), higher diastolic blood pressure (P = 0.008), higher levels of Interleukin (IL)-6 (P < 0.001), Leptin (P = 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P = 0.049) and thyroid stimulating hormone (TSH) (P = 0.004) in blood serum compared with subjects without pathological periodontal pockets (PD ≥ 4 mm; n = 61). The bivariate linear regression analysis demonstrated that PD ≥ 4 mm (P = 0.008) and systolic blood pressure (P < 0.001) were significantly associated with the dependent variable "diastolic blood pressure". The association between PD ≥ 4 mm and diastolic blood pressure remained significant (P = 0.006) even after adjusting for potential confounders BMI-sds, age, gender, mother's country of birth, BOP >25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis.. In conclusion, this study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.

Topics: Adolescent; Age Factors; Body Mass Index; Chemokine CCL2; Child; Cross-Sectional Studies; Dental Plaque Index; Diastole; Female; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Obesity; Periodontal Index; Periodontal Pocket; Pilot Projects; Sex Factors; Systole; Thyrotropin

Hypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease. It has been reported recently that hypertensive patients and animals are characterized by decreased density of arterioles and capillaries in the tissues, called rarefaction. Rarefaction significantly increases peripheral resistance which results in elevated blood pressure, leads to vessel damage and induction of inflammation. Therefore, we hypothesized that hypertension is associated with decreased serum concentration of physiological pro-angiogenic factors and concomitant increased production of angiogenesis inhibitors.. 82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to measure serum levels of the following cytokines: endostatin, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF).. Hypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. In addition, hypertension was associated with decreased levels of physiological pro-angiogenic mediators such as: angiogenin and bFGF. The hypertensive group was also characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of inflammation.. Presented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Endostatins; Female; Fibroblast Growth Factor 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Interleukin-8; Male; Middle Aged; Ribonuclease, Pancreatic; Vascular Endothelial Growth Factor A; Young Adult

Obesity and hypertension have been recognized as inflammatory diseases capable of activating the immune system, thus contributing to an increased cardiovascular risk. However, the link between adaptive immunity, obesity, and hypertension is poorly understood. We investigated the relationship of the body mass index (BMI) on the inflammatory, vascular, and immune responses in patients with hypertension naïve of anti-hypertensive treatment. Hypertensive patients (N = 88) were divided into three groups: normal weight (NW), overweight (OW), and obese (OB) subjects. Anti-oxidized LDL autoantibodies (anti-oxLDL Abs), anti-ApoB-D peptide (anti-ApoB-D) Abs, interleukin (IL)-8 and IL-10, flow-mediated dilation (FMD) of the brachial artery, and 24-h ambulatory blood pressure monitoring (ABPM) were assessed. OB patients presented lower levels of anti-oxLDL Abs and IL-10, higher levels of IL-8, and impaired FMD, when compared to NW and OW (P < 0.05), without differences between groups regarding anti-ApoB-D Abs. After adjusting for age, systolic and diastolic blood pressure, anti-oxLDL Abs were inversely correlated with BMI and waist circumference (r = -0.24, P = 0.02 and r = -0.25, P = 0.02, respectively), whereas ApoB-D correlated with 24-h ABPM (r = 0.22, P = 0.05 for systolic, and r = 0.29, P = 0.01 for diastolic blood pressure). Regression analyses showed inverse associations of anti-oxLDL Abs with BMI (β = -0.05, P = 0.01) and waist circumference (β = -0.01, P = 0.02); anti-ApoB-D Abs were associated with systolic and diastolic 24-h ABPM (β = 0.96, P = 0.04; β = 1.02, P = 0.005, for systolic and diastolic 24-h ABPM, respectively). Among hypertensive patients, obesity modulates the immune and inflammatory milieu, determining an unfavorable balance of cytokines and reduction in titers of anti-oxLDL Abs. Twenty-four hour ABPM is associated with titers of anti-ApoB-D Abs.

Topics: Adult; Aged; Antihypertensive Agents; Apolipoproteins B; Apolipoproteins D; Autoantibodies; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Interleukin-10; Interleukin-8; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Monitoring, Ambulatory; Obesity

A total of 98 patients with chronic obstructive pulmonary disease, arterial hypertension and combined flow of both chronic obstructive pulmonary disease and arterial hypertension were examined. The patients were divided into 3 groups. The first group included patients with arterial hypertension, the second consisted of patients with COPD, the third of patients with combined flow of COPD and AH. ELISA method was used to determine serum concentrations of interleukin-6 and tumor necrosis factor-α. Immunoturbidimetric method was used to measure the concentration of C-reactive protein. Spectrophotometrically markers of oxidative stress, the levels of oxidative protein modifications were measured. It was found that there was a significant increase in levels of interleukin-6, tumor necrosis factor-α and C-reactive protein in patients with combined flow of chronic obstructive pulmonary disease and arterial hypertension while comparing with other groups. In patients with comorbid disorders COPD and AH an increase in products of oxidative modification of proteins, spontaneous and iron induced aldehydephenylhydrazone's and ketondinitrophenylhydrazone's were also observed. Significant correlations between biomarkers of systemic inflammation and oxidative stress were found.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Comorbidity; Female; Humans; Hypertension; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Oxidative Stress; Pneumonia; Proteins; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

To explore the role and mechanism of Duffy antigen receptor for chemokines (DARC) of tissue in promoting the inflammatory reaction of the limb with venous hypertension.. moral arteriovenous fistula was surgically created to establish the rat model of venous hypertension. A total of 36 SD rats were randomly divided into pcDNA3.1-DARC (Group A), empty plasmid of pcDNA3.1 (Group B) and control (Group C) groups. The animals were sacrificed at Days 14 and 42 post-operation respectively. The expressions of DARC at the RNA and protein level were detected by real-time polymerase chain reaction (PCR) and Western blot. And the serum level of interleukin (IL)-8 was detected by enzyme linked immunosorbent assay (ELISA) and the degrees of apoptosis and leukocytic infiltration of local tissue were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and hematoxylin and eosin (HE) staining.. With the elapsing time of venous hypertension, the DARC expression in tissue, the extent of apoptosis and leukocytic infiltration in tissue showed an increasing trend in Groups A and B. Group A was obviously higher than Group B during the corresponding period. And the differences were statistically significant (P < 0.05). The serum levels of IL-8 of Groups A and B showed a decreasing trend. And Group A was obviously lower than Group B. Both groups were higher than the control group. The differences were statistically significant (P < 0.05).. The level of DARC in tissue and the degree of inflammatory reaction of venous hypertension have a positive correlation. And DARC may promote the development of venous hypertension inflammation through augmenting the adhesion and migration of leukocytes.

Topics: Animals; Duffy Blood-Group System; Hypertension; Interleukin-8; Phlebitis; Rats; Rats, Sprague-Dawley; Receptors, Antigen; Receptors, Chemokine; Venous Pressure

In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

Topics: Aged; Biomarkers; Coronary Sinus; Extracellular Matrix; Female; Humans; Hypertension; Inflammation; Interleukin-6; Interleukin-8; Male; Natriuretic Peptide, Brain; Ultrasonography; Ventricular Remodeling

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms. We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean ± sd MSNA increased across the exposure (17.2 ± 5.1 versus 21.7 ± 7.3 bursts·min⁻¹; p < 0.01) and baroreflex control of sympathetic outflow declined from -965.3 ± 375.1 to -598.4 ± 162.6 AIU·min⁻¹ ·mmHg⁻¹ (p < 0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Topics: Adiponectin; Adult; Blood Pressure; Body Mass Index; C-Reactive Protein; Chemokine CCL5; Female; Humans; Hypertension; Hypoxia; Intercellular Adhesion Molecule-1; Interleukin-8; Leptin; Male; Receptors, Interleukin-1; Sleep Apnea Syndromes; Sympathetic Nervous System; Tumor Necrosis Factor-alpha

To investigate whether concurrent hypertension affects vitreous cytokine levels in diabetic retinopathy.. Vitreous samples from 41 patients with diabetic retinopathy with or without concurrent hypertension, who underwent vitrectomy, were collected. Vitreous cytokine concentrations were simultaneously measured using flow cytometry. Patients were stratified according to hypertension or other clinical conditions, and the differences in vitreous levels of monocyte chemotactic protein 1, interleukin 8, vascular endothelial growth factor, interferon-inducible protein 10, and monokine induced by interferon gamma were examined.. Vitreous levels of monocyte chemotactic protein 1 and interleukin 8 were significantly (P < 0.05) higher in hypertensive patients than in nonhypertensive patients and were significantly (P < 0.05) higher in active diabetic retinopathy than in inactive diabetic retinopathy. Vitreous levels of vascular endothelial growth factor, interferon-inducible protein 10, and monokine induced by interferon gamma were not affected by the coexistence of hypertension. In multivariate models, active diabetic retinopathy (P = 0.004 and P = 0.007), systolic blood pressure (P = 0.039 and P = 0.041), and hypertension (P = 0.032 and P = 0.035) were significant and independent predictors for increased vitreous monocyte chemotactic protein 1 and interleukin 8 levels.. Both monocyte chemotactic protein 1 and interleukin 8 levels were elevated in the vitreous of patients with diabetic retinopathy and concurrent hypertension. These findings may help to explain the epidemiologic and clinical evidence that systemic hypertension exacerbates diabetic retinopathy.

Topics: Adult; Aged; Chemokine CCL2; Chemokine CXCL10; Diabetic Retinopathy; Female; Fluorescein Angiography; Humans; Hypertension; Immunoassay; Interleukin-8; Male; Middle Aged; Monokines; Vascular Endothelial Growth Factor A; Vitrectomy; Vitreous Body

Hypertension is one of the main drivers of the heart failure (HF) epidemic. The aims of this study were to profile fibro-inflammatory biomarkers across stages of the hypertensive heart disease (HHD) spectrum and to examine whether particular biochemical profiles in asymptomatic patients identify a higher risk of evolution to HF.. This was a cross-sectional observational study involving a population of 275 stable hypertensive patients divided into two different cohorts: Group 1, asymptomatic hypertension (AH) (n= 94); Group 2, HF with preserved ejection fraction  (n= 181). Asymptomatic hypertension patients were further subdivided according to left atrial volume index ≥34 mL/m(2) (n= 30) and <34 mL/m(2) (n= 64). Study assays involved inflammatory markers [interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein 1 (MCP1), and tumour necrosis factor α], collagen 1 and 3 metabolic markers [carboxy-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 1, amino-terminal propeptide of collagen 3 (PIIINP), and carboxy-terminal telopeptide of collagen 1 (CITP)], extra-cellular matrix turnover markers [matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and tissue inhibitor of metalloproteinase 1 (TIMP1)], and the brain natriuretic peptide. Data were adjusted for age, sex, systolic blood pressure, and creatinine. Heart failure with preserved ejection fraction  was associated with an increased inflammatory signal (IL6, IL8, and MCP1), an increased fibrotic signal (PIIINP and CITP), and an increased matrix turnover signal (MMP2 and MMP9). Alterations in MMP and TIMP enzymes were found to be significant indicators of greater degrees of asymptomatic left ventricular diastolic dysfunction.. These data define varying fibro-inflammatory profiles throughout different stages of HHD. In particular, the observations on MMP9 and TIMP1 raise the possibility of earlier detection of those at risk of evolution to HF which may help focus effective preventative strategies.

Topics: Aged; Biomarkers; Chemokine CCL2; Cross-Sectional Studies; Diastole; Echocardiography, Doppler; Female; Heart Atria; Heart Failure; Humans; Hypertension; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Tissue Inhibitor of Metalloproteinase-1; Ventricular Dysfunction, Left; Ventricular Remodeling

Accumulating evidence suggests that inflammation as well as oxidative stress play essential roles in atherogenesis, progression of atherosclerosis, and plaque instability and rupture. Recent studies on available anti-hypertensive agents have focused on their anti-atherosclerotic effects over and above their blood pressure lowering action. These studies have included investigations on several types of calcium channel blockers, with several investigations indicating that a dihydropiridine-based calcium channel blocker, azelnidipine, developed in Japan, has unique anti-oxidative properties. An anti-inflammatory effect of azelnidipine has, however, yet to be established and therefore we carried out a series of in vivo and in vitro studies to investigate this possibility. This was achieved by measuring inflammatory and oxidative stress markers in 16 high risk hypertensive patients administered 16mg/day of azelnidipine. After 4 weeks of treatment, serum levels of hsCRP, IL-6, and IL-8 and urinary 8-OHdG were decreased significantly, despite blood pressure remaining unchanged. Cultures of human mononuclear leukocytes collected from six healthy volunteers showed 100 nM of azelnidipine caused significant inhibition of formyl-methyonyl leucyl phenylalanine (fMLP)-induced production of IL-8. Taken together, these results suggest that azelnidipine has anti-inflammatory effects independent of its anti-hypertensive action. As leukocytes do not possess voltage-operated calcium channels, the effect of azelnidipine in these cells appears to occur independently of an L-type calcium channel antagonizing effect.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Atherosclerosis; Azetidinecarboxylic Acid; Biomarkers; C-Reactive Protein; Calcium Channel Blockers; Deoxyguanosine; Dihydropyridines; Female; Humans; Hypertension; In Vitro Techniques; Inflammation Mediators; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Oxidative Stress

To explore the cardiovascular diseases marker gene expression profile of the familial aggregation hypertension patients,and to screen differentially expressed genes.. The patients who had directly related family members for more than three generations suffering from hypertension were selected as experiment group, and healthy individuals as control group. Oligo GEArray gene chip technique was used to detect the expression of cardiovascular diseases marker gene in peripheral blood. The ratio of positive/negative standard value >2.0, or ≤0.5 and >0 was identified as differential gene.. Compared with control group, there were 10 up-regulated differential genes in experiment group, composing genes involved in lipid metabolism, immune response-related molecules, cell adhesion molecules, extracellular molecules and coagulation, including apolipoprotein E (ApoE), epithelial V-like antigen-1 (EVA-1), interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-8, integrin-β1 (ITGB-1), matrix metalloproteinase-9 (MMP-9), nuclear factor-ΚB (NF-ΚB), platelet endothelial cell adhesion molecule-1 (PECAM-1), selectin-P (SEL-P). There were 3 down-regulated genes, including coagulation factors-III (F-III), lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), and serine protease inhibitor-1 (SERPINE-1).. This study suggested that familial aggregation hypertension related to a variety of gene markers of cardiovascular disease, especially elements concerning coagulation and extracellular protease inhibitor-related genes.

Topics: Biomarkers; Case-Control Studies; Humans; Hypertension; Interferon-gamma; Interleukin-1beta; Interleukin-8; Matrix Metalloproteinase 9; NF-kappa B; Oligonucleotide Array Sequence Analysis; Platelet Endothelial Cell Adhesion Molecule-1; Transcriptome

Chemokines promote vascular inflammation and play a pathogenic role in the development and maintenance of hypertension. In the present study, the expression of the chemokine interleukin-8/CXCL8 (IL-8/CXCL8) was investigated in cultured vascular smooth muscle cells (VSMC) obtained from the thoracic aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). IL-8/CXCL8 expression in thoracic aorta tissue and VSMC in SHR were significantly higher than in WKY. However, the expression of CXCR1 mRNA in VSMC from WKY was higher than that in VSMC from SHR. Angiotensin II (Ang II) induced a higher level of IL-8/CXCL8 mRNA expression in VSMC from SHR than in VSMC from WKY. The time course of Ang II-induced IL-8/CXCL8 expression in VSMC from SHR correlated with those of Ang II-induced CXCL1 and Ang II type 1 (AT1) receptor expression, and the expression of IL-8/CXCL8 by Ang II was inhibited by the AT1 receptor antagonist losartan. The effect of Ang II on IL-8/CXCL8 expression was not dependent on nuclear factor-kappaB (NF-kappaB) activation, but was mediated by an extracellular signal-regulated kinase (ERK) signaling pathway. Although Ang II directly induced IL-8/CXCL8 expression, expression of Ang II-induced IL-8/CXCL8 decreased in VSMC transfected with heme oxygenase-1. These results suggest that IL-8/CXCL8 plays an important role in the pathogenesis of Ang II-induced hypertension and vascular lesions in SHR.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Cells, Cultured; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Heme Oxygenase-1; Hypertension; Interleukin-8; Losartan; Male; Muscle, Smooth, Vascular; NF-kappa B; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Signal Transduction; Transfection; Up-Regulation; Vasoconstrictor Agents

Atherosclerotic plaques prone to cause thrombotic complications and plaque rupture account for the majority of fatal myocardial infarctions (MI), which may be complicated by ventricular fibrillation (VF). Matrix-degrading metalloproteinases (MMPs) and their inhibitors (TIMPs) are expressed in atherosclerotic lesions and contribute to plaque vulnerability. Interleukin-8 (IL-8) is one of the predominant chemokines interacting with MMPs and TIMPs and the coagulation system. The aim of the present study was to assess potential differences of levels of MMP-9, TIMP-1 and IL-8 in postmyocardial infarction patients with or without VF complicating acute MI.. Blood samples were taken from 45 patients with VF complicating acute MI and from 88 patients without VF. All samples were collected during a symptom-free interval remote from the acute ischemic event with a median of 556 days. The markers of interest were TIMP-1, MMP-9 and IL-8.. IL-8 and TIMP-1 levels were significantly higher among patients with VF than among patients without VF (p<0.001). In a logistic regression approach IL-8 was an independent indicator of patients prone to VF during MI (p=0.03). High levels of TIMP-1 (p=0.05), MMP-9 (p=0.03), the MMP-9/TIMP-1 ratio (p=0.049) and hypertension (p=0.02) were found to be indicators in patients with reinfarction or unstable angina pectoris during follow-up. Hypertension (p=0.02) and MMP-9 (p=0.03) were the only significant indicators characterizing patients undergoing coronary reinterventions, such as percutaneous coronary interventions and coronary bypass surgery.. Higher TIMP-1 and IL-8 levels are present in patients with VF complicating MI. High TIMP-levels may be related to the degree of fibrosis which is a substrate for electrical instability and may contribute to the occurrence of VF. Patients prone to develop VF during MI seem to have an increased proinflammatory condition compared to patients without VF.

Topics: Aged; Biomarkers; Humans; Hypertension; Interleukin-8; Matrix Metalloproteinase 9; Middle Aged; Myocardial Infarction; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Ventricular Fibrillation

Insulin resistance and central obesity are often associated with hypertension. The metabolic syndrome is a cluster of these common clinical disorders, and is related with an increased risk for cardiovascular diseases. A number of pro-inflammatory cytokines derived from adipose tissues have been thought to contribute to the development of insulin resistance and accelerated atherosclerosis. Among them, TNF-alpha has been most widely studied; it not only suppresses the insulin signaling, but also elicits vascular inflammation. Indeed, inhibition of TNF-alpha was found to improve insulin resistance in obese rats and reduce the progression of atherosclerosis in apolipoprotein E knockout mice, respectively. These observations demonstrate that TNF-alpha could play a central role in the pathogenesis of insulin resistance and accelerated atherosclerosis in the metabolic syndrome. Considering that the primary goals of treatment for hypertensive patients with the metabolic syndrome are prevention of the development of diabetes and cardiovascular events, anti-hypertensive drugs that have abilities to block the TNF-alpha signaling would be desirable as a first-line therapy for these patients. In the process of the search for such a unique anti-hypertensive drug, we have recently found that azelnidipine, a newly developed and commercially used long-acting dihydropyridine-based calcium antagonist (DHP), inhibited TNF-alpha-induced activator protein-1 activation and interleukin-8 expression in human umbilical vein endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation. The concentration of azelnidipine that was found effective in these in vitro-experiments is well within the therapeutic range. Since endothelial cells do not possess voltage-operated L-type calcium channels, these observations suggest that the beneficial effects of azelnidipine are not likely due to calcium channel blocking property, but due to its unique anti-oxidative ability. Furthermore, we have very recently found that serum levels of monocyte chemoattractant protein-1, a biomarker for subclinical atherosclerosis, were significantly decreased by the treatment of azelnidipine in patients with essential hypertension. In this paper, we would like to hypothesize that due to its unique TNF-alpha signal modulatory, anti-oxidative property, azelnidipine may be a promising DHP that targets diabetes and cardiovascular diseases in hypertensive patients with the metabolic synd

Topics: Antihypertensive Agents; Antioxidants; Arteriosclerosis; Azetidinecarboxylic Acid; Biomarkers; Calcium; Cardiovascular Diseases; Cells, Cultured; Chemokine CCL2; Diabetes Mellitus; Dihydropyridines; Endothelium, Vascular; Humans; Hypertension; Insulin Resistance; Interleukin-8; Models, Biological; Reactive Oxygen Species; Transcription Factor AP-1; Tumor Necrosis Factor-alpha; Umbilical Veins

The pathogenic mechanisms underlying the increase in peripheral resistance and the contraction of smooth muscular fibre cells in essential hypertension are not yet clearly understood. However, it is now known that immune system activation plays a role in the pathogenesis of some forms of arterial hypertension, and recent data show that the Ca2+ influx in some cells (i.e. red blood cells, leukocytes, platelets, smooth muscular fibre cells) is increased in subjects with essential hypertension, thus revealing a possible alteration in cellular membrane. The end-points of this study were therefore to ascertain whether red blood cells used as a cellular membrane model have a greater Ca2+ dependent K+ flow (Gardos effect) in hypertensive patients than in normotensive controls, to point out a different regulation of ionic channels, and whether IL-8 and the adhesion molecule ICAM-1 influence the membranous outflow.. The study was conducted on 87 Caucasian subjects. Of these, 50 (25 men, 25 women; mean age 43 +/- 3 years, mean body mass index (BMI) 27 +/- 0.5 and 22.3 +/- 0.3 kg/m(2), respectively) had mild-to-moderate hypertension (mean arterial blood pressure 120 +/- 8 mmHg ). The other 37 (18 men, 19 women; mean age 39 +/- 3 years; BMI 23.8 +/- 0.5 kg/m(2) and 22.8 +/- 0.5 kg/m(2), respectively were normotensive healthy volunteers (mean arterial blood pressure 89 +/- 2 mmHg). All the patients and subjects were untreated for at least 4 weeks before blood sampling.. Ca2+-dependent K+ outflow was found to be greater in samples from patients with essential hypertension than in those from normotensive controls. lL-8 and ICAM-1 significantly enhanced the Ca2+-dependent K+ outflow in red blood cells from hypertensive subjects but had an inhibitory effect on cells from controls. In the experimental model, the presence of TMB-8, a membrane calcium antagonist, significantly reduced the Ca2+-dependent K+ efflux.. Vasoconstriction in subjects with essential hypertension may therefore depend on a different regulation of ionic flow that probably supports an increased Ca2+ inflow in smooth muscle fibre cells. Under certain pathological conditions, some immune system components (i.e. interleukins, adhesion molecules) may directly enhance membrane permeability to Ca2+, thus inducing vasoconstriction in the smooth muscle cells.

Topics: Adult; Calcium; Calcium Channel Blockers; Erythrocyte Membrane; Female; Gallic Acid; Humans; Hypertension; Intercellular Adhesion Molecule-1; Interleukin-8; Male; Potassium; Potassium Channels; Vasoconstriction

To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB.. Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization.. Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation.. Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.

Topics: Abdomen; Animals; Compartment Syndromes; Hypertension; Interleukin-8; Male; Neutrophils; NF-kappa B; Rabbits; Shock, Hemorrhagic

To study the role of IL-8 in predicting future coronary artery disease (CAD) in apparently healthy men and women.. A nested case-control study was performed in the prospective EPIC-Norfolk population study. We measured baseline IL-8 concentrations among 785 apparently healthy individuals in whom fatal or nonfatal CAD developed during follow-up and 1570 matched controls. Baseline IL-8 concentrations were higher in cases than in matched controls (3.5 pg/mL versus 3.1 pg/mL, P=0.001). The risk of future CAD increased with increasing quartiles of IL-8 (P linearity <0.0001). Among individuals in the highest IL-8 quartile, the unadjusted odds ratio for future CAD was 1.72 (95% CI, 1.34 to 2.21; P<0.0001). The odds ratio for future CAD was still significant after adjustment for traditional risk factors (OR, 1.58; 95%CI, 1.19 to 2.09; P=0.002) and after additional adjustment for C-reactive protein and white cell count (OR, 1.77; 95% CI, 1.21 to 2.60; P=0.001).. We conclude that among apparently healthy men and women, elevated levels of IL-8 are associated with an increased risk of future CAD. These prospective data support a role for IL-8 in the development of CAD events.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Comorbidity; Coronary Disease; England; Female; Humans; Hypertension; Interleukin-8; Interleukins; Leukocyte Count; Lipids; Lipoproteins; Male; Middle Aged; Obesity; Odds Ratio; Predictive Value of Tests; Prospective Studies; Risk; Risk Factors; Smoking; Tumor Necrosis Factor-alpha

According to increasing experimental and clinical evidence the inflammatory processes take important part in the development of atherosclerosis and its complications. The aim of the study was to evaluate the concentrations of selected inflammatory (IL-6, IL-8, MCP-1 and TNF-alpha) and antiinflammatory (IL-10) cytokines in children and adolescents with atherosclerosis risk factors: obesity, hypertension and diabetes. We studied 64 children and adolescents aged 14.88 +/- 2.4 years. Children were divided into: group with obesity (n = 11), group with obesity accompanying by hypertension (n = 14), children with hypertension (n = 11) and diabetic group (n = 28). Control group consisted of 15 healthy children aged 15.3 yrs. The evaluation of studied cytokines was performed with the use of immunoenzymatic ELISA kits (R&D Systems). IL-6 concentration in the whole group was 5.7 +/- 19 pg/mL and was significantly higher than in controls--2.3 +/- 2.3 pg/mL (p = 0.04). The highest IL-6 level was found in obesity group--11 +/- 30 pg/mL (p = 0.02). Significant difference was also found in the group with obesity and hypertension--8.3 +/- 15 pg/mL (p = 0.046) and in diabetic children--6.5 +/- 14 pg/ml (0.046). Interleukin 8 level in whole group was 486 +/- 839 pg/mL and was not different from the control group--236 +/- 197 pg/mL. IL-10 level in the study group was 4.9 +/- 3 pg/mL and did not differ from controls--4.5 +/- 1.2 pg/mL. TNF-alpha level was significantly higher in whole study group--8.9 +/- 2.4 pg/mL (p = 0.04) compared to controls--8.0 +/- 4.9 pg/mL, and in children with obesity--9.5 +/- 1.5 pg/mL (p = 0.034) as well as in children with obesity and hypertension--9.6 +/- 3.1 pg/mL (p = 0.042). MCP-1 level did not differ between the studied groups (228 +/- 124 pg/mL in whole study group) and controls--182 +/- 46 pg/mL. Correlation analysis by Spearman showed significantly correlation between IL-6 and body mass index in the whole study group. TNF-alpha also correlated with body mass index.. Children and adolescents with obesity, obesity accompanying by hypertension and diabetes have elevated levels of IL-6 and TNF-alpha. IL-6 and TNF-alpha correlates with body mass index not only in obese but also in hypertensive, slim children. The elevated levels of cytokines (IL-6, TNF-alpha) in children with atherosclerosis risk factors (particularly obesity) can confirm the presence of inflammatory process in early phases of atherosclerosis.

Topics: Adolescent; Body Mass Index; Case-Control Studies; Chemokine CCL2; Child; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Interleukin-10; Interleukin-6; Interleukin-8; Male; Obesity; Risk Factors; Tumor Necrosis Factor-alpha

Hypertension is a risk factor for coronary heart disease. Macrophages are critically involved in both atherogenesis and plaque instability. Although macrophages may be subjected to excess mechanical stress in these diseases, the way in which biomechanical forces affect macrophage function remains incompletely defined.. To investigate the molecular response to mechanical force in macrophages.. We used a DNA microarray with 1056 genes to describe the transcriptional profile of mechanically induced genes in human monocytic THP-1 cells. Mechanical deformation was applied to a thin and transparent membrane on which cells were cultured. After THP-1 cells were pre-incubated in the presence of phorbol 12-myristate 13-acetate (0.2 micromol/l) for 24 h, THP-1 cells attached to the membrane were subjected to biaxial mechanical strain. Interleukin-8 concentrations were determined using an enzyme-linked immunosorbent assay.. In DNA microarray analysis, cyclic mechanical strain at 1 Hz induced only three genes more than 2.5-fold at 3 and 6 h in THP-1 cells: prostate apoptosis response-4 (3.0-fold at 3 h, 6.7-fold at 6 h), interleukin-8 (4.3-fold at 6 h) and the immediate-early response gene, IEX-1 (2.6-fold at 6 h). Real-time reverse transcriptase polymerase chain reaction analysis confirmed the amplitude-dependent induction of these three genes. In addition, mechanical strain increased interleukin-8 protein expression.. The present study demonstrates that human monocytic cells respond to mechanical deformation with induction of immediate-early and inflammatory genes. These findings suggest that mechanical stress in vivo, such as that associated with hypertension, may play an important part in atherogenesis and instability of coronary artery plaques, through biomechanical effects on vascular macrophages.

Topics: Apoptosis Regulatory Proteins; Arteriosclerosis; Carrier Proteins; Cell Line; Gene Expression; Gene Expression Profiling; Humans; Hypertension; Immediate-Early Proteins; Interleukin-8; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins; Membrane Proteins; Monocytes; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stress, Mechanical

Therapy for deep vein thrombosis (DVT) resolution in those patients in whom a complication or contraindication to anticoagulation occurs is limited. As prior work suggests that thrombus maturation involves early influx of neutrophils (PMN) and neovascularization, we hypothesized that administering the proinflammatory/proangiogenic chemokine interleukin (IL)-8 might accelerate thrombus resolution.. An established rodent model of DVT (inferior vena cava [IVC] ligation) was used whereby daily intravenous recombinant human IL-8 (1 microg) or vehicle control was administered, with sacrifice at 4 and 8 days. Prior to sacrifice and at harvest, duplex ultrasound of the DVT and femoral venous pressure measurements were performed. Thrombi were analyzed by immunohistochemical techniques for PMN, monocytes, and neovascularization; for chemokines, by enzyme-linked immunoassay; and fibrosis, by hydroxyproline assay and trichrome staining.. IL-8 accelerated thrombus dissolution 4 days after IVC ligation, with 6-fold increased thrombus blood flow by duplex ultrasound and a 23% increased absolute femoral venous pressure compared with controls (both P < 0.05). These findings may be partially explained by the fact that animals receiving IL-8, as compared with controls, had 2.5-fold greater thrombus neovascularization (with a trend continuing to 8 days) and increased PMN at 4 days. Thrombus vascular endothelial growth factor was significantly reduced at 8 days postligation, while monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha were not altered by IL-8 administration. At 8 days post-IVC-ligation, fibrosis was 12-fold greater with IL-8 treatment compared with controls.. A proinflammatory/proangiogenic thrombus milieu, as conferred by IL-8, enhances thrombus resolution and underscores the important relationship between neovascularity and inflammation.

Topics: Animals; Chemokines; Endothelial Growth Factors; Fibrosis; Hypertension; Interleukin-8; Leukocyte Count; Lymphokines; Male; Neovascularization, Physiologic; Neutrophils; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Venous Pressure; Venous Thrombosis

In the serum of woman during the pregnancy with and without PIH the activity of interleukin-8 and myeloperoxydase was measured. 40 pregnant woman with PIH and 16 normal pregnant woman were included in the study. We have not found significative difference between examined populations.

Topics: Adult; Blood Pressure; Enzyme-Linked Immunosorbent Assay; Female; Gestational Age; Humans; Hypertension; Interleukin-8; Peroxidase; Pregnancy