interleukin-8 and Vascular-Diseases

COVID‑19 patients with severe infection have been observed to have elevated auto‑antibodies (AAs) against angiotensin II receptor type 1 (AT1R) and endothelin (ET) 1 receptor type A (ETAR), compared with healthy controls and patients with favorable (mild) infection. AT1R and ETAR are G protein‑coupled receptors, located on vascular smooth muscle cells, fibroblasts, immune and endothelial cells, and are activated by angiotensin II (Ang II) and ET1 respectively. AAs that are specific for these receptors have a functional role similar to the natural ligands, but with a more prolonged vasoconstrictive effect. They also induce the production of fibroblast collagen, the release of reactive oxygen species and the secretion of proinflammatory cytokines (including IL‑6, IL‑8 and TNF‑α) by immune cells. Despite the presence of AAs in severe COVID‑19 infected patients, their contribution and implication in the severity of the disease is still not well understood and further studies are warranted. The present review described the major vascular homeostasis systems [ET and renin‑angiotensin‑aldosterone system (RAAS)], the vital regulative role of nitric oxide, the AAs, and finally the administration of angiotensin II receptor blockers (ARBs), so as to provide more insight into the interplay that exists among these components and their contribution to the severity, prognosis and possible treatment of COVID‑19.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Collagen; COVID-19; Endothelial Cells; Endothelins; Humans; Interleukin-6; Interleukin-8; Nitric Oxide; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, Endothelin A; Receptors, Angiotensin; Tumor Necrosis Factor-alpha; Vascular Diseases

Small vessel disease (SVD) and neuroinflammation both occur in Alzheimer disease (AD) and other neurodegenerative diseases. It is unclear whether these processes are related or independent mechanisms in AD, especially in the early stages of disease. We therefore investigated the association between white matter lesions (WML; the most common manifestation of SVD) and CSF biomarkers of neuroinflammation and their effects on cognition in a population without dementia.. Individuals without dementia from the Swedish BioFINDER study were included. The CSF was analyzed for proinflammatory markers (interleukin [IL]-6 and IL-8), cytokines (IL-7, IL-15, and IL-16), chemokines (interferon γ-induced protein 10, monocyte chemoattractant protein 1), markers of vascular injury (soluble intercellular adhesion molecule 1, soluble vascular adhesion molecule 1), and markers of angiogenesis (placental growth factor [PlGF], soluble fms-related tyrosine kinase 1 [sFlt-1], vascular endothelial growth factors [VEGF-A and VEFG-D]), and amyloid β (Aβ)42 Aβ40, and p-tau217. WML volumes were determined at baseline and longitudinally over 6 years. Cognition was measured at baseline and follow-up over 8 years. Linear regression models were used to test associations.. A total of 495 cognitively unimpaired (CU) elderly individuals and 247 patients with mild cognitive impairment (MCI) were included. There was significant worsening in cognition over time, measured by Mini-Mental State Examination, Clinical Dementia Rating, and modified preclinical Alzheimer composite score in CU individuals and patients with MCI, with more rapid worsening in MCI for all cognitive tests. At baseline, higher levels of PlGF (β = 0.156,. Most neuroinflammatory CSF biomarkers were associated with WML in individuals without dementia. Our findings especially highlight a role for PlGF, which was associated with WML independent of Aβ status and cognitive impairment.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Female; Humans; Inflammation; Interleukin-16; Interleukin-8; Neuroinflammatory Diseases; Placenta Growth Factor; tau Proteins; Vascular Diseases; Vascular Endothelial Growth Factor A; White Matter

Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer's disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined. Its correlations with inflammatory cytokines in cognitive impairment also await investigation. 80 subjects with no cognitive impairment (NCI), 160 with CIND and 144 with dementia were included in a cross-sectional study on a Singapore-based memory clinic cohort. All subjects underwent comprehensive clinical, neuropsychological and brain neuroimaging assessments, together with clinical diagnoses based on established criteria. Blood samples were collected and OPN as well as inflammatory cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF) were measured using immunoassays. Multivariate regression analyses showed significant associations between increased OPN and VCI groups, namely CIND with CeVD, AD with CeVD and VaD. Interestingly, higher OPN was also significantly associated with AD even in the absence of CeVD. We further showed that increased OPN significantly associated with neuroimaging markers of CeVD and neurodegeneration, including cortical infarcts, lacunes, white matter hyperintensities and brain atrophy. OPN also correlated with elevated levels of IL-6, IL-8 and TNF. Our findings suggest that OPN may play a role in both VCI and neurodegenerative dementias. Further longitudinal analyses are needed to assess the prognostic utility of OPN in disease prediction and monitoring.

Topics: Aged; Alzheimer Disease; Atrophy; Biomarkers; Brain; Case-Control Studies; Cerebrovascular Disorders; Cognition; Cognitive Dysfunction; Cohort Studies; Cross-Sectional Studies; Dementia, Vascular; Female; Humans; Interleukin-6; Interleukin-8; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Osteopontin; Singapore; Tumor Necrosis Factor-alpha; Vascular Diseases

Duffy antigen / receptor for chemokines (DARC) possesses high affinity for several chemokine subgroups of CC and CXC. Although DARC has been shown to play a role in many inflammatory diseases, its effect on chronic venous disease (CVD) remains unidentified. We explored whether the expression of DARC in skin tissue was activated under venous hypertension as well as the relationships between DARC and inflammation.. The inflammation in a rat model of venous hypertension caused by a femoral arterial-venous fistula (AVF) was studied. At specified intervals the pressure in the femoral veins was recorded within 42 days. Hindlimb skin specimens were harvested at different time points. The expressions of DARC, interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in skin tissue were examined. Mononuclear cells infiltrated in skin tissue were detected.. Femoral venous pressures in AVF groups increased significantly at different time points (P < 0.01). DARC was expressed in skin tissue and its expression level increased significantly in AVF groups from the 7nd day on and was enhanced in a time-dependent manner within 42 days (P < 0.05). Meanwhile, both MCP-1 and IL-8 had higher levels, accompanied by increased mononuclear cells infiltrating into skin tissue (P < 0.05).. A rat AVF model which can maintain venous hypertension for at least 42 days is competent for researching the pathogenesis of CVD. DARC, which plays a role in the inflammation of skin tissue under venous hypertension, may become a new molecular target for diagnosis and treatment of CVD at a very early stage.. Hintergrund: Duffy-Antigen / Rezeptor für Chemokine (DARC) weist eine hohe Affinität zu mehreren Chemokin-Untergruppen von CC und CXC auf. Es hat sich zwar gezeigt, dass DARC bei vielen entzündlichen Erkrankungen eine Rolle spielt, aber dessen Einfluß auf die chronische Venenkrankheit ist unbekannt. Neben den Beziehungen zwischen DARC und Entzündung haben wir auch untersucht, ob die Expression von DARC im Hautgewebe unter venöser Hypertonie aktiviert wurde. Material und Methoden: Es wurde die Entzündung bei einem Rattenmodell mit venöser Hypertonie auf Grund einer arteriovenösen Fistel (AVF) am Oberschenkel untersucht. Regelmäßig wurde während 42 Tagen der Blutdruck in Beinvenen erfasst. Probenahme erfolgte zu verschiedenen Zeitpunkten an der Haut des Hinterbeins. Die Expression von DARC, Interleukin-8 (IL-8) und von monozytenchemotaktischen Protein-1 (MCP-1) im Hautgewebe wurden untersucht ebenso wie ins Hautgewebe eingeschleuste Leukozyten. Ergebnisse: Der Venendruck am Oberschenkel hat sich zu verschiedenen Zeitpunkten bei den AVF Tieren erheblich erhöht (P < 0.01). DARC-Expression erfolgt im Hautgewebe und dessen Expressionsniveau erhöhte sich bei AVF-Gruppen ab Tag 7 erheblich, und zwar tendenziell steigend in einer zeitabhängigen Art und Weise innerhalb von 42 Tagen (P < 0.05). Inzwischen erreichten MCP-1 und IL-8 ein noch höheres Niveau, während die Anzahl ins Hautgewebe eingeschleuster Leukozyten auch zunahm (P < 0.05). Schlussfolgerungen: Ein Rattenmodell mit AVF, das für mindestens 42 Tage eine venöse Hypertonie aufrecht erhalten kann, eignet sich für die Untersuchung der Pathogenese der chronischen Venenkrankheit. Die DARC-Expression, die in der Entzündung des Hautgewebes unter venöser Hypertonie eine Rolle spielt, könnte zu einem neuen molekularen Ziel der frühzeitigen Diagnose und Behandlung werden.

Topics: Animals; Arteriovenous Shunt, Surgical; Chemokine CCL2; Chronic Disease; Disease Models, Animal; Duffy Blood-Group System; Femoral Artery; Femoral Vein; Inflammation; Interleukin-8; Male; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface; Skin; Time Factors; Up-Regulation; Vascular Diseases; Venous Pressure

Our previous studies indicated that zinc induced inflammatory response in both vascular endothelial cells and promonocytes. Here, we asked if other metals could cause the similar effect on vascular endothelial cells and tried to determine its underlying mechanism. Following screening of fifteen metals, zinc and nickel were identified with a marked proinflammatory effect, as determined by ICAM-1 and IL-8 induction, on human umbilical vein endothelial cells (HUVECs). Inhibiting protein expression of myeloid differentiation primary response protein-88 (MyD88), a Toll-like receptor (TLR) adaptor acting as a TLR-signaling transducer, significantly attenuated the zinc/nickel-induced inflammatory response, suggesting the critical roles of TLRs in the inflammatory response. Blockage of TLR-4 signaling by CLI-095, a TLR-4 inhibitor, completely inhibited the nickel-induced ICAM-1 and IL-8 expression and NFκB activation. The same CLI-095 treatment significantly blocked the zinc-induced IL-8 expression, however with no significant effect on the ICAM-1 expression and a minor inhibitory effect on the NFκB activation. The finding demonstrated the differential role of TLR-4 in regulation of the zinc/nickel-induced inflammatory response, where TLR-4 played a dominant role in NFκB activation by nickel, but not by zinc. Moreover, inhibition of NFκB by adenovirus-mediated IκBα expression and Bay 11-7025, an inhibitor of cytokine-induced IκB-α phosphorylation, significantly attenuated the zinc/nickel-induced inflammatory responses, indicating the critical of NFκB in the process. The study demonstrates the crucial role of TLRs in the zinc/nickel-induced inflammatory response in vascular endothelial cells and herein deciphers a potential important difference in NFκB activation via TLRs. The study provides a molecular basis for linkage between zinc/nickel exposure and pathogenesis of the metal-related inflammatory vascular disease.

Topics: Adenoviridae; Human Umbilical Vein Endothelial Cells; Humans; I-kappa B Proteins; Intercellular Adhesion Molecule-1; Interleukin-8; Myeloid Differentiation Factor 88; NF-kappa B; NF-KappaB Inhibitor alpha; Nickel; Signal Transduction; Sulfonamides; Toll-Like Receptor 4; Vascular Diseases; Zinc

In patients with atrial septal defect in whom pulmonary hypertension could develop as a consequence of left-to-right shunt, the extent of neutrophil-mediated lung injury induced by cardiopulmonary bypass (CPB) is related to the degree of increase in the preoperative pulmonary artery pressure. In the present study, we investigated the relationship between levels of granulocyte elastase (GEL) after CPB and preoperative pulmonary hemodynamics or changes in pulmonary function after the operation in patients with mitral valve disease, in whom pulmonary hypertension could develop as a result of pulmonary venous congestion. The plasma levels of GEL were measured before and after CPB in patients who underwent mitral valve replacement. Respiratory index (RI) was evaluated preoperatively and postoperatively. Preoperative pulmonary hemodynamics were determined within one month of the operation. Granulocyte elastase level rose significantly after CPB from baseline (134.3 +/- 44.6 mg/L versus 2042.1 +/- 1215.0 mg/L; p <0.001). Peak level of GEL was significantly correlated with preoperative systolic pulmonary artery pressure (r = 0.71; p = 0.020), mean pulmonary artery pressure (r = 0.64; p = 0.046), pulmonary capillary wedge pressure (r = 0.68; p = 0.032), and pulmonary-to-systemic arterial pressure ratio (r = 0.64; p = 0.045), but not with the hemodynamic variables for pulmonary blood flow or pulmonary resistance. Moreover, the value of (Postoperative RI - Preoperative RI)/Preoperative RI was positively correlated with the peak level of GEL (r = 0.76; p = 0.011). In conclusion, in patients with mitral valvular disease, as in those with atrial septal defect, the increase in GEL level after CPB is proportional to the increase in preoperative pulmonary artery pressure, which may cause the accordant pulmonary vascular damage.

Topics: Aged; Cardiopulmonary Bypass; Female; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Interleukin-6; Interleukin-8; Intraoperative Period; Leukocyte Elastase; Lung Diseases; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Stenosis; Predictive Value of Tests; Pulmonary Circulation; Vascular Diseases

Proinflammatory cytokines play key roles in atherogenesis and disease progression. Because hyperhomocysteinemia is an independent risk factor for cardiovascular disease, we hypothesized that homocysteine could be atherogenic by altering the expression of specific cytokines in vascular endothelial cells.. Northern blot and RNase protection assays showed that DL-homocysteine induced mRNA expression of the proinflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured human aortic endothelial cells (HAECs). Homocysteine had no effect on expression of other cytokines, namely tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interleukin-1beta, and transforming growth factor-beta. MCP-1 mRNA expression increased 1 hour after homocysteine treatment, reached a maximum within 2 to 4 hours, and declined to basal levels over the next 24 hours. Induction of mRNA expression for both chemokines was observed with as little as 10 micromol/L DL-homocysteine, and maximal expression was achieved with 50 micromol/L DL-homocysteine. Homocysteine also triggered the release of MCP-1 and IL-8 protein from HAECs into the culture medium. The induction was specific for homocysteine, because equimolar concentrations of L-homocystine, L-cysteine, and L-methionine had no effect on mRNA levels and protein release. Furthermore, L-homocysteine induced chemokine expression, but D-homocysteine did not, thus demonstrating enantiomeric specificity. The culture medium from homocysteine-treated HAECs promoted chemotaxis in human peripheral blood monocytes and U937 cells. Anti-human recombinant MCP-1 antibody blocked the migration.. Pathophysiological levels of L-homocysteine alter endothelial cell function by upregulating MCP-1 and IL-8 expression and secretion. This suggests that L-homocysteine may contribute to the initiation and progression of vascular disease by promoting leukocyte recruitment.

Topics: Aorta, Thoracic; Blotting, Northern; Cells, Cultured; Chemokine CCL2; Chemotaxis; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Homocysteine; Humans; Interleukin-8; RNA, Messenger; Sulfur Compounds; Time Factors; U937 Cells; Vascular Diseases