leukotriene-b4 and Cardiovascular-Diseases

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease of multiple joints that puts the patient at high risk for developing cardiovascular diseases (CVDs). The aim of the present study was to conduct an up-to-date systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess potential changes in RA disease activity, inflammation, and CVD risk after oral intake of ω-3 polyunsaturated fatty acids.. Publications up to July 31, 2016 were examined using the PubMed, SCOPUS, and EMBASE databases.. English language; human subjects; both sexes; RCTs; oral intake of ω-3 fatty acids; minimum duration of 3 mo; and no medication change throughout intervention. The Cochrane Risk of Bias tool was used to assess quality of trials. We included 20 RCTs, involving 717 patients with RA in the intervention group and 535 RA patients in the control group.. The beneficial properties of ω-3 polyunsaturated fatty acids on RA disease activity confirm the results of previous meta-analyses. Among five proinflammatory markers evaluated, only leukotriene B4 was found to be reduced. However, a positive effect on blood lipid profile of patients with RA was evident, perhaps for the first time.

Topics: Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Fatty Acids, Omega-3; Humans; Leukotriene B4; Randomized Controlled Trials as Topic; Triglycerides

Leukotriene B

Topics: Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Arthritis; Cardiovascular Diseases; Flap Endonucleases; Humans; Leukotriene B4; Neoplasms; Neutrophils; Pulmonary Disease, Chronic Obstructive; Structure-Activity Relationship

Leukotrienes are potent inflammatory mediators synthesized locally within the cardiovascular system through the 5-lipoxygenase pathway of arachidonic acid metabolism. The leukotrienes, consisting of dihydroxy leukotriene LTB4 and the cysteinyl leukotrienes LTC4, LTD4 and LTE4, act by targeting cell surface receptors expressed on inflammatory cells and on structural cells of vessel walls. LTB, induces leukocyte activation and chemotaxis via high- and low-affinity receptor subtypes (BLT1 and BLT2), respectively. Recently, BLT, receptors were found on human vascular smooth muscle cells, inducing their migration and proliferation. Cysteinyl leukotrienes are vasoconstrictors and induce endothelium-dependent vascular responses through the CysLT, and CysLT2 receptor subtypes. There is also pharmacological evidence for the existence of further CysLT receptor subtypes. Taken together, experimental and genetic studies suggest a major role of leukotrienes in atherosclerosis and in its ischemic complications such as acute coronary syndromes and stroke. Furthermore, the effects on vascular smooth muscle cells suggest a role in the vascular remodeling observed after coronary angioplasty, as well as in aortic aneurysm. Further experimental and clinical studies are needed to determine the potential of therapeutic strategies targeting the leukotriene pathway in cardiovascular disease.

Topics: Angioplasty, Balloon, Coronary; Animals; Aortic Aneurysm; Arachidonic Acid; Atherosclerosis; Cardiovascular Diseases; Cell Movement; Coronary Restenosis; Disease Models, Animal; Guinea Pigs; Humans; Hypertension; Leukotriene Antagonists; Leukotriene B4; Leukotriene C4; Leukotriene D4; Leukotriene E4; Leukotrienes; Mice; Muscle, Smooth, Vascular; Rats; Receptors, Leukotriene; Stroke

Our current understanding of the physiology of the leukotrienes is far from complete. The abundant supply of synthetic products has directed researchers into examining what the mediators affect rather than the basic mechanism studies of their involvement in disease. It is clear that the peptide leukotrienes possess potent constrictor actions of the microvasculature and can enhance permeability. These actions alone represent a new avenue of interpreting pathologic processes and could lead to alternate means of treating certain diseases in the future. It is of special interest that a consistent action of the leukotrienes is to reduce coronary blood flow, decrease myocardial contractility, and reduce cardiac output without affecting the heart rate. This profile of action is the first indication that a mediator can play a significant role in unstable angina. The main physiologic actions of the leukotrienes in the cardiovascular system are currently believed to be associated with episodes of ischemia and shock. Their relative contribution to the shock states, especially when compared with the actions of other known mediators of shock such as the prostaglandins, thromboxane, angiotensin, serotonin, and histamine, awaits clarification. LTB4 is a proinflammatory mediator that has opened a completely new perspective on the physiologic role of phagocytic cells. Novel therapeutic approaches to inflammatory-related diseases may result from an inhibition of cell chemokinesis, aggregation, and degranulation. The role of LTB4 in the immune system awaits further clarification.

Topics: Animals; Blood Platelets; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cerebrovascular Circulation; Coronary Disease; Coronary Vasospasm; Humans; Leukotriene B4; Lung; Muscle Contraction; Muscle, Smooth, Vascular; Neutrophils; Skin; SRS-A; Thromboxane A2

The leukotrienes (LTs) are 5-lipoxygenase metabolites of arachidonic acid. The synthesis and release of LTs have been demonstrated in many cells and organs, and LTs are considered to be normal products of continuous metabolism of arachidonic acid. However, although evidence in favor of a critical role for LTs in regulation of physiological functions is still scarce, a growing body of evidence suggests a role for LTs in mediation of several pathophysiological processes such as generalized or local immune reactions, inflammation, asthma, shock, and trauma. LTs have been shown to have potent actions on many essential organs and systems, including the cardiovascular system (heart, blood vessels, microcirculation), the pulmonary system (lung, airways), the central nervous system (neural, glial, and vascular elements), the gastrointestinal tract, and the immune system. In these organs the effects of LTs are mediated by specific LT receptors. Identification of LTs and characterization of their regional and systemic pathological effects, together with characterization of their receptors and elucidation of their structure-activity relationships, are fundamental to developing LT antagonists or synthesis inhibitors that might prevent or reverse LT-dependent reactions. Preliminary reports have already shown that such pharmacological agents ameliorate some aspects of disease processes in experimental animals as well as in humans. In this brief review we intend to highlight the evidence that implicates LTs in normal physiological functions as well as in disease processes.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Central Nervous System; Central Nervous System Diseases; Humans; Hypersensitivity; Inflammation; Leukotriene B4; Respiration Disorders; Respiratory Physiological Phenomena; SRS-A; Vasomotor System; Wounds and Injuries

Although prostaglandin research began about 50 years ago, many of the most important advances in understanding the biochemistry, physiology and pharmacology have taken place within the past five to ten years. There is great potential for the extension of this research to the clinical practice of medicine. At this time, the most common interaction that clinicians have with the prostaglandin field is in administering nonsteroidal anti-inflammatory drugs, which function by inhibiting prostaglandins. The uses of these drugs include treating not only inflammation, but also dysmenorrhea, some renal disease, thrombotic diseases and some metabolic disorders. Prostaglandin analogs, with their potent effects on uterine contraction, are in common use in obstetrics. Other analogs, with gastric and duodenal cytoprotective effects are useful in treating peptic ulcer disease. Future benefits from prostaglandin and leukotriene research may include new therapy for inflammatory and hypersensitivity diseases such as asthma, inflammatory bowel diseases and dermatitis.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Diseases; Chemical Phenomena; Chemistry; Digestive System; Digestive System Physiological Phenomena; Female; Humans; Immunity, Cellular; Inflammation; Kidney; Leukotriene B4; Lung; Lung Diseases; Male; Metabolic Diseases; Pregnancy; Prostaglandin Antagonists; Prostaglandins; Reproduction; SRS-A; Thromboxanes; Uterine Contraction

Prostaglandins, thromboxanes and leukotrienes are oxygen metabolites of arachidonic acid forming a family of lipidic substances with intrinsic biological activities. The significance of biosynthesis of these mediators in response to cell stimulation remains unclear. Numerous data suggest that these compounds, produced by blood cells and vascular cells, play an important role in cardiovascular pathology, allergy or inflammation. The concept, based on biochemistry, of distinct metabolic pathways should be reappraised, using a physiological approach that involves a biological effect resulting from a synergistic action of different compounds. The development of specific assay methods will permit to investigate compounds obtained from biological fluids or from cells present in recognized pathological situations. Such in vitro data should help to clarify the role of these autacoids in cardiovascular, allergic or inflammatory diseases.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cardiovascular Diseases; Humans; Hypersensitivity; Inflammation; Leukotriene B4; Lipoxygenase; Prostaglandin-Endoperoxide Synthases; Prostaglandins; SRS-A; Thromboxanes

Topics: Adolescent; Alprostadil; Animals; Arachidonic Acids; Blood Pressure; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Epoprostenol; Hemodynamics; Humans; Hypertension; Leukotriene B4; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Rats; Renal Circulation; SRS-A; Stress, Psychological; Thromboxanes

Although substantial variation exists in individual responses to omega-3 (ω-3) (n-3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase-dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P < 0.001). Compliance was equivalent (∼88%), whereas decreases in plasma triglycerides and VLDL particle sizes and reductions in stimulated monocyte leukotriene B4 production were larger in the high-response group. Although total diet quality scores were similar, the low-response group showed lower estimated 2005 Healthy Eating Index subscores for dark-green and orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements. This trial was registered at clinicaltrials.gov as NCT00536185.

Topics: Adult; Arachidonate 5-Lipoxygenase; Black or African American; Cardiovascular Diseases; Cholesterol, VLDL; Diet; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Energy Intake; Erythrocytes; Fatty Acids, Omega-3; Feeding Behavior; Female; Humans; Leukotriene B4; Linear Models; Lipoproteins; Male; Middle Aged; Monocytes; Patient Compliance; Surveys and Questionnaires; Triglycerides; Vegetables

Cardiovascular risk depends largely on paraoxonase (PON-1) and apolipoprotein A4 (APOA4) gene polymorphisms. To compare the effects of consumption of walnut-enriched meat versus low-fat meat (LM) on selected soluble adhesion molecules and leukotrienes (LTB4).. In all 22 subjects at increased cardiovascular risk were taken. It is a non-blinded, cross-over, placebo-controlled study. Two 5-week experimental periods separated by 4-6 week wash-out interval. Participants consumed walnut-enriched meat during one period and LM during the other. Diet characteristics, HDLc, Apo A1, paraoxonase, sVCAM-1, sICAM-1 and LTB4 were analysed. PON-1 55, PON-1 192 and APOA4 360 polymorphism effects were also assessed.. Individuals consuming walnut-enriched meat displayed higher paraoxonase activity (P<0.001), lower levels of sICAM and aVCAM (P=0.046, P=0.012, respectively) and leukotriene B4 (P=0.044), and lower paraoxonase-1/HDLc and paraoxonase-1/Apo A1 ratios (both, P<0.001) than those consuming LM. Paraoxonase levels correlated negatively with those of sICAM (r=-0.471, P<0.01). Significant decreases (at least P<0.05) were observed in sICAM concentrations in PON-1 55LM+MM, PON-1 QQ192 and APOA4-2 carriers while decreases in sVCAM in QR+RR and APOA4-1 carriers were observed. Paraoxonase-1/HDLc and paraoxonase-1/Apo A1 ratios were significantly influenced by paraoxonase polymorphisms.. Walnut-enriched meat appears as a functional meat as consumed in the framework of a mix diet lowered the concentration of some selected inflammatory chemoattractant biomarkers. This effect was largely influenced by PON-1 and Apo A4-360 polymorphisms.

Topics: Apolipoprotein A-I; Apolipoproteins A; Aryldialkylphosphatase; Cardiovascular Diseases; Cell Adhesion Molecules; Cholesterol, HDL; Diet; Female; Food, Fortified; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Juglans; Leukotriene B4; Male; Meat; Middle Aged; Nuts; Plant Preparations; Polymorphism, Genetic; Risk Factors; Vascular Cell Adhesion Molecule-1

Although both chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CVD) are characterised by chronic, systemic inflammation, their reciprocal interactions are poorly understood. The purpose of this study was to determine the concentrations of both inflammatory and oxidative stress biomarkers in the serum and exhaled breath condensate (EBC) of COPD patients, either with coexisting CVD or without cardio-vascular comorbidities.. Twenty-four COPD patients with CVD were allocated to group A, 20 COPD patients without CVD were assigned to group B and 16 healthy patients were included as a control. A medical history and physical examination were performed, and the following were measured: serum CRP concentration, glucose level, uraemic acid level and lipid profile. In addition 8-isoprostane, LTB4 and IL-8 concentrations were measured both in serum and EBC. Spirometry, six-minute walk test and echocardiography were performed in all subjects.. EBC concentrations of 8-isoprostane and LTB4, and serum levels of CRP, 8-soprostane, LTB4, IL-8 were significantly higher in COPD patients than in healthy controls. COPD patients with CVD were not found to have higher concentrations of the assessed markers than those without CVD, neither in the serum nor EBC. CRP, 8-isoprostane and LTB4 levels in serum, and IL-8 concentration in EBC correlated negatively with the value of forced expiratory volume in one second.. Although systemic inflammation coexists with COPD, it is not elevated in COPD patients with CVD. Since this phenomenon may result from treatment with statins, future studies should state whether COPD patients could benefit from the additional statin therapy.

Topics: Aged; Biomarkers; Breath Tests; Cardiovascular Diseases; Comorbidity; Dinoprost; Female; Humans; Inflammation Mediators; Interleukin-8; Leukotriene B4; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive

 Inflammation and oxidative stress play an essential role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD)..  The aim of the study was to evaluate the echocardiographic parameters of the left and right ventricular functions in patients with COPD with or without CVD and in healthy controls, and to establish their relationships with biomarkers of inflammation and oxidative stress..  The study included 24 patients with COPD and CVD, 20 patients with COPD, and 16 healthy controls. Physical examination, spirometry, and echocardiography were performed in all participants, and blood samples were collected. The levels of 8‑isoprostane, leukotriene B4, and interleukin 8 were determined in the blood and exhaled breath condensate (EBC)..  In patients with COPD, the left ventricular ejection fraction was lower than in healthy controls (58.84% ±9.57% vs. 65.50% ±3.35%, P <0.01); moreover, it was lower in patients with COPD and CVD than in those without comorbidities (54.29% ±10.58% vs. 64.30% ±3.74%, P <0.01). The systolic and diastolic functions of the right ventricle were lower in patients with COPD than in the control group, while systolic pulmonary arterial pressure was significantly higher in patients with COPD than in the control group (37.04 ±7.6 mmHg vs. 28.12 ±4.44 mmHg, P = 0.01). Some echocardiographic parameters of the left and right ventricular functions correlated with the concentrations of inflammatory markers both in serum and EBC..  The echocardiographic parameters of cardiac function correlate with the markers of inflammation in patients with COPD, which emphasizes the inflammatory background of CVD.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Diastole; Dinoprost; Echocardiography; Female; Heart Ventricles; Humans; Inflammation; Interleukin-8; Leukotriene B4; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Systole; Ventricular Function, Left; Ventricular Function, Right

Whereas circulating levels of C-reactive protein (CRP) have been associated with, for example, arterial stiffness, subclinical atherosclerosis and metabolic syndrome, other inflammatory biomarkers with potential interest for these conditions may not be measurable systemically. The predictive value of salivary biomarkers in these contexts has remained largely unexplored. The aim of the present study was to establish the association of different salivary biomarkers of inflammation with subclinical cardiovascular disease.. Two hundred and fifty-nine individuals were included in the study. Saliva and plasma samples were collected, and each individual underwent carotid ultrasound and measures of pulse wave velocity and blood pressure. Medical history of previous cardiovascular disease, current medications and smoking were collected by questionnaire.. Salivary levels of CRP, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), matrix metalloproteinase 9 (MMP-9), creatinine and lysozyme were measured. Salivary levels of CRP were significantly correlated with plasma levels (r = 0.73, P < 0.0001). In an age-adjusted and sex-adjusted analysis, salivary CRP was significantly and positively correlated with mean arterial blood pressure, pulse pressure, pulse wave velocity, BMI, metabolic syndrome, waist-to-hip ratio and intima-media thickness. Increasing age and sex-adjusted salivary CRP tertiles were in addition associated with carotid plaques. In a multivariate analysis, CRP and MMP-9 were associated with intima-media thickness, LTB4 and PGE2 with arterial stiffness, and lysozyme with hypertension.. Saliva may represent an alternative mean for evaluation of cardiovascular risk.

Topics: Aged; Atherosclerosis; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Creatinine; Dinoprostone; Female; Humans; Hypertension; Inflammation Mediators; Leukotriene B4; Male; Matrix Metalloproteinase 9; Metabolic Syndrome; Middle Aged; Muramidase; Pulse Wave Analysis; Risk Factors; Saliva; Vascular Stiffness; Waist-Hip Ratio

Leukotrienes (LT) play a role in inflammation, cardiovascular diseases, and cancer. Although some studies suggest that there are genes that determine variability of some LT-related phenotypes, the genetic influence on these phenotypes has not been evaluated.. The relative contributions of genetic and environmental influences to the 5-lipoxygenase pathway-related phenotypes (5-Lipoxygenase, five lipoxygenase activating protein (FLAP), LTA(4)-hydrolase and LTC(4)-synthase expression, and LTB(4)-plasma concentration and LTB(4) production by stimulated whole blood) were assessed in a sample of 934 individuals in 35 extended families. Our design is based on extended families recruited through a probands with idiopathic thrombophilia. This strategy allows us the analysis of the effects of measured covariates (such as sex, age and smoking), genes, and environmental variables shared by members of a household.. All of these phenotypes showed significant genetic contributions, with heritabilities ranging from 0.33 to 0.51 for enzyme expression and from 0.25 to 0.50 for LTB(4) production of the residual phenotypic variance. Significant phenotypic and genetic correlation among the LT-related traits was found. More importantly, FLAP and LTA(4)-hydrolase expression exhibit significant genetic correlations with arterial thrombosis, indicating that some of the genes that influence quantitative variation in these phenotypes also influence the risk of thrombosis.. This is the first study that quantifies the genetic component of 5-Lipoxygenase pathway phenotypes. The high heritability of these traits and the significant genetic correlations between arterial thrombosis and some of these phenotypes suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.

Topics: 5-Lipoxygenase-Activating Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Arachidonate 5-Lipoxygenase; Cardiovascular Diseases; Child; Child, Preschool; Epoxide Hydrolases; Female; Genetic Predisposition to Disease; Glutathione Transferase; Humans; Leukotriene B4; Male; Middle Aged; Phenotype; Risk Factors; Spain; Thrombophilia

Elevated cholesteryl ester transfer protein (CETP) activity has been reported in type 1 diabetic subjects and may be one cause of the high incidence of macrovascular complications in these patients. LDL delivers arachidonic acid (AA), in the form of cholesteryl ester (CE), to cells such as monocytes and fibroblasts, as precursor for eicosanoid synthesis. We discovered that AA content in LDL CE was significantly correlated with CETP activity, even after controlling for CETP concentration, in type 1 diabetic children. The production of LTB(4), a potent chemotactic and pro-inflammatory factor which plays a role in atherogenesis, has been shown to be increased in type 1 diabetic patients. We hypothesized that in these subjects, increased AA content in LDL CE, resulting from increased CETP activity and transient hyperinsulinemia, may lead to enhanced synthesis of LTB(4) and subsequently the higher incidence of cardiovascular disease.

Topics: Arachidonic Acid; Blood Glucose; Cardiovascular Diseases; Carrier Proteins; Cholesterol Ester Transfer Proteins; Cholesterol Esters; Diabetes Mellitus, Type 1; Eicosanoids; Glycoproteins; Humans; Hyperinsulinism; Insulin; Leukotriene B4; Lipoproteins, LDL; Models, Biological