Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.
J Mol Cell Cardiol 2006 Apr
PMID:Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines. 1651 15

Pediatric cardiac surgery with cardiopulmonary bypass (CPB) induces a complex inflammatory response that may cause multiorgan dysfunction. The objective of this study was to measure postoperative cytokine production and correlate the magnitude of this response with intraoperative variables and postoperative outcomes. Serum samples from 20 children (median age, 15 months) undergoing cardiac surgery with CPB were obtained preoperatively and on postoperative days (POD) 1-3. Serum levels of interleukin (IL)-6, IL-8, and IL-10 increased significantly on POD 1 (p < 0.01) vs pre-op values to 271 +/- 68, 44 +/- 9, 7.5 +/- 0.8 pg/ml, respectively, whereas serum IL-1beta, IL-12, and tumor neurosis factor -alpha were not significantly changed. The serum IL-6 and IL-8 levels correlated positively (p < 0.01) with the degree of postoperative medical intervention as measured by the Therapeutic Interventional Scoring System and indicated a greater need for inotropic support (p = 0.057). A negative correlation (p < 0.01) between IL-6, IL-8, and mixed venous oxygen saturation suggested compromised cardiopulmonary function. Patients with single ventricle anatomy had the highest levels of IL-6 and IL-8 (629 +/- 131 and 70 +/- 17 pg/ml, respectively), with a mean CPB time of 106 +/- 23 minutes. Thus, the proinflammatory response after surgery with CPB was associated with postoperative morbidity with increased need for medical intervention.
Pediatr Cardiol
PMID:Cytokine response in children undergoing surgery for congenital heart disease. 1683 75

Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. The mechanism(s) by which acute and chronic myocardial ischemia translate into the characteristic features of ischemic cardiomyopathy is unresolved at present. We hypothesized that such translation relates to modification of specific gene expression programs during acute and chronic ischemic insults to the myocardium. Global mRNA expression profiles by Affymetrix HG_U133A GeneChip analysis on 33 samples was performed on non-failing human left ventricular myocardium during acute and chronic ischemia in 6 patients undergoing coronary artery by-pass grafting. Results were confirmed by real-time quantitative RT-PCR in 14 patients and supported by histology and immunohistochemistry analyses. Acute ischemia elicited an acute inflammatory response including IL-6, IL-8, MCP-1, VCAM-1 and CYR-61 with an attenuated increase of IL-6 and IL-8 in chronic ischemic myocardium compared to normal myocardium. High mRNA expression of connective tissue growth factor (CTGF) was present in chronic ischemic myocardium with a high degree of correlation between CTGF and mRNA expression of specific genes (e.g. thrombospondin 4, collagen type Ialpha2, versican, adlican, latent transforming growth factor beta binding protein 2 and fibronectin) involved in extracellular matrix remodelling. In conclusion, acute inflammatory induction (e.g. IL-8, IL-6, VCAM-1 and MCP-1) and an acute phase CCN family gene with effects on matrix interactions (CYR-61) might play important roles in the coupling between acute ischemic episodes and chronic myocardial remodelling. In addition, the findings support an important role of CTGF signalling in chronic extracellular matrix remodelling in chronic coronary artery disease.
J Mol Cell Cardiol 2007 Apr
PMID:Gene expression signals involved in ischemic injury, extracellular matrix composition and fibrosis defined by global mRNA profiling of the human left ventricular myocardium. 1734 75

CD34+ progenitor cells hold promise for therapeutic neovascularization in various settings. In this study, the role of human peripheral blood CD34+ cells in neovascularization and inflammatory cell recruitment was longitudinally studied in vivo. Human CD34+ cells were incorporated in Matrigel, implanted subcutaneously in nude mice, and explanted after 2, 4, 7, or 14 days. Cell-free Matrigels served as controls. Histochemical analyses demonstrated that neovascularization occurred almost exclusively in CD34+ implants. Cellular and capillary density were increased in cell-loaded Matrigels after 2 days and further increased at 14 days. Human CD34+ cells did not incorporate in neovessels, but formed vWF+/CD31+/VEGF+ cell clusters that were present up to day 14. However, CD34+ cells induced host neovascularization, as demonstrated by increased presence of murine CD31+ and vWF+ vasculature from day 7 to 14. Moreover, recruitment of murine monocytes/macrophages was significantly enhanced in CD34+ implants at all time points. Gene expression of chemotactic cytokines MCP-1 and IL-8 was detected on CD34+ cells in vitro and confirmed immunohistochemically in cell-loaded explants at all time points. Our data indicate that human CD34+ cells, implanted in a hypoxic environment, generate an angiogenic niche by secreting chemotactic and angiogenic factors, enabling rapid neovascularization, possibly via recruitment of monocytes/macrophages.
J Mol Cell Cardiol 2007 Jun
PMID:Circulating human CD34+ progenitor cells modulate neovascularization and inflammation in a nude mouse model. 1749 Jun 80

The impressive correlation between cardiovascular disease and alterations in glucose metabolism has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes, and matrixins are prepro enzymes responsible for the timely breakdown of extracellular matrix. Interleukins (ILs) are classified based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin acts on both diseases in the same direction - regardless if harmful, favorable or neutral. They are clustered into three groups: noxious (the 'bad', 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the 'good', 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and 'aloof' , comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering and IL-30 through 33 were not included due to the scarce available data. It may be seen that (1) favorable effects of a given interleukin on either diabetes or atherosclerosis predicts similar effects on the other; (2) equally, harmful interleukin effects on one disease can be extrapolated to the other, and (3) absence of influence of a given interleukin on one of these diseases forecasts lack of effects on the other. Matrixins seem to present a similar pathophysiological pattern. These facts further support the unifying etiologic theory of diabetes and heart disease, emphasizing the importance of a cardiovascular diabetologic approach to these cytokines for future research. A pharmacologic simultaneous targeting of interleukins and matrixins might provide an effective means to concurrently control both atherosclerosis and diabetes.
Adv Cardiol 2008
PMID:Biomarkers in cardiovascular diabetology: interleukins and matrixins. 1823 Sep 55

Monocytes/macrophages and lymphocytes have a key role in the pathogenesis of atherosclerosis through the production of inflammatory and anti-inflammatory cytokines. We evaluated mRNA expression and protein production of CCL2, CXCL8, CXCL9, CXCL10, IFN-gamma and IL-10 in vitro as well as the expression of the CCR2 and CXCR3 receptors in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy controls in the presence or absence of oxidized LDL (oxLDL). Patients with CAD showed higher constitutive expression of CCL2, CXCL8, CXCL9, CXCL10 and IFN-gamma mRNA and, after stimulation with oxLDL, higher expression of CCL2 and CXCL8 mRNA than the control group. We also detected higher levels of CCL2 and CXCL8 in supernatants of oxLDL-stimulated PBMCs from CAD patients than in corresponding supernatants from controls. Patients with CAD had a higher percentage of constitutive CCR2(+) and CXCR3(+) cells after stimulation with oxLDL. Among CAD patients, the main differences between the stable (SA) and unstable angina (UA) groups were lower IL-10 mRNA production in the latter group. Altogether, our data suggest that PBMCs from CAD patients are able to produce higher concentrations of chemokines and cytokines involved in the regulation of monocyte and lymphocyte migration and retention in atherosclerotic lesions.
Int J Cardiol 2009 Jul 24
PMID:Differential expression of cytokines, chemokines and chemokine receptors in patients with coronary artery disease. 1861 79

Long-term neurodevelopmental sequelae are commonly detectable in children after open-heart surgery with cardiopulmonary bypass (CPB). The objective of the study was to determine the neurodevelopmental outcome in these children in relation to postoperative inflammatory reaction. This is a prospective, observational study on children with congenital heart defects (n = 32) undergoing elective open-heart surgery in a tertiary pediatric cardiac center. Neurodevelopmental outcome was assessed in the median 6 months after CPB. Neurological examination was done in all children before the operation and, additionally, complete neurodevelopmental status was assessed preoperatively in 14 children. Three hours after the end of CPB, plasma concentrations of interleukin (IL)-6 and IL-8 were strongly elevated (p < 0.001). Moreover, there was a rise of neutrophils and C-reactive protein at 24 h postoperatively (p < 0.001). Intellectual performance after surgery was correlated with preoperative performance, r ( S ) = 0.83, p < 0.001 (mean IQ scores after CPB = 90.4 +/- 18.4 and before CPB = 87.5 +/- 14.5, p = 0.20). Multiple regression analysis demonstrated that preoperative IQ scores accounted for 83.8% of the variance of postoperative IQ scores (p < 0.0001). Inflammatory variables were not significant predictors of postoperative IQ scores. The frequency of neuromotor abnormalities at 6 months after CPB was influenced by the presence of a cyanotic heart defect, duration of CPB and aortic clamp time, and plasma levels of IL-6 shortly after CPB (R (2) = 67.8%, p = 0.002). In conclusion, in the examined population, preexisting neurodevelopmental impairment is frequent and predicts postoperative outcome. The high frequency of postoperative neuromotor disabilities seems to be associated with the type of congenital heart defect but also with the procedure and possible complications of CPB.
Pediatr Cardiol 2009 Apr
PMID:Inflammatory response and neurodevelopmental outcome after open-heart surgery in children. 1908 40

Current evidence supports that inflammation is a major driving force underlying the initiation of coronary plaques, their unstable progression, and eventual disruption; patients with a more pronounced vascular inflammatory response have a poorer outcome. Biomarkers are generally considered to be proteins or enzymes - measured in serum, plasma, or blood - that provide independent diagnostic and prognostic value by reflecting an underlying disease state. In the case of coronary artery disease (CAD), inflammatory biomarkers, have been extensively investigated; more evidence exists for C-reactive protein (CRP). Using high sensitivity (hs) assays, epidemiologic data demonstrate an association between hs-CRP and risk for future cardiovascular morbidity and mortality among those at high risk or with documented CAD. Moreover, a series of prospective studies provide consistent data documenting that mild elevation of baseline levels of hs-CRP among apparently healthy individuals is associated with higher long-term risk for cardiovascular events. Yet, the predictive value of hs-CRP is found to be independent of traditional cardiovascular risk factors. Recent studies suggest that, besides CRP, other inflammatory biomarkers such as cytokines [interleukin (IL)-1, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1)], soluble CD40 ligand, serum amyloid A (SAA), selectins (E-selectin, P-selectin), myeloperoxidase (MPO), matrix metalloproteinases (MMPs), cellular adhesion molecules [intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1)], placental growth factor (PlGF) and A(2) phospholipases may have a potential role for the prediction of risk for developing CAD and may correlate with severity of CAD. Finally, indications suggest that the increased risk associated with inflammation may be modified with certain preventive therapies and biomarkers may help to identify the individuals who would benefit most from these interventions.
J Cardiol 2009 Jun
PMID:Inflammatory biomarkers in coronary artery disease. 1978 79

Abdominal aortic aneurysm is a multifactorial disease with genetic risk factors and an immunologic component. Immune cells, including macrophages, neutrophils, mast cells, B- and T- lymphocytes, along with vascular smooth muscle cells and adventitial fibroblasts, produce cytokines and enzymes, promoting an inflammatory reaction, extracellular matrix degradation, and neovascularization. Among the different enzymes secreted by immune and stromal cells, matrix metalloproteinase (MMP)-2, MMP-9, MMP-12, cathepsins, and neutrophil elastase cause medial degeneration. Chymase causes smooth muscle cell apoptosis, and MMP-3, MMP-8, and MMP-13 cause adventitial collagen degradation, promoting abdominal aortic aneurysm rupture. At the same time chemokines (interleukin 8, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein-1) cause recruitment and proliferation of inflammatory cells, whereas cytokines (vascular endothelial growth factor and transforming growth factor-beta) promote neoangiogenesis.
Cardiol Rev
PMID:Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. 1969 Apr 70

Open heart surgery supported by cardiopulmonary bypass is associated with heart and lung ischemia-reperfusion injury (IRI). Limb remote ischemic preconditioning (RIPC) reduces injury caused by ischemia-reperfusion in multiple distant organs. We conducted a prospective clinical trial (randomized and controlled) to test the feasibility and safety of limb RIPC, as well as its protective effects against myocardial and pulmonary IRI for infants undergoing repair of simple congenital heart defects. Infants undergoing repair of ventricular septal defects were enrolled in our study and randomly assigned to one of two treatment groups: limb RIPC or control. RIPC was induced twice (24 h and 1 h preoperatively) via three 5-min cycles of ischemia and reperfusion on the left upper arm using a blood pressure cuff. Lung compliance, respiratory index (RI), and cardiac inotropic score (IS) were calculated for each patient. Serum concentrations of the following factors were measured perioperatively: interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha; lactate dehydrogenase (LDH), creatine kinase (CK), and its isoenzyme (CK-MB), and troponin I (TnI); malondialdehyde (MDA) and superoxide dismutase (SOD). The expression of heat shock protein 70 (HSP 70) in cardiomyocytes was analyzed by Western blot. Surgical outcomes, including limb movement and sensory function, were recorded in detail. Sixty infants weighting less than 7 kg were studied, with 30 patients in the RIPC group and 30 in the control group. Within 6 months of discharge from the hospital, no limb disability, sensory disturbance, or other surgical complications were found in any patient. Compared with the control group, patients in the RIPC group had higher Cs and Cd, along with lower RI and IS at various postoperative phases. At the beginning of the operation, serum concentrations of IL-6, IL-8, IL-10, TNF-alpha, LDH, CK, and TnI were higher in the RIPC group than the control group. Postoperatively, release of cytokines and leakage of heart enzymes were attenuated in the RIPC group; serum concentrations of cytokines and heart enzymes were lower in the RIPC group at some, but not all, postoperative time points. Furthermore, the RIPC group had lower coronary sinus venous concentrations of MDA and higher concentrations of SOD. Similarly, the expression of HSP 70 was upregulated in cardiomyocytes from the RIPC group. Limb RIPC can be applied safely and easily in infants, can attenuate systemic inflammatory response syndrome, and can increase systemic tolerance to IRI, imparting a protective effect against myocardial and pulmonary IRI. The expression of HSP 70 has an important role in the mechanism of action for RIPC.
Pediatr Cardiol 2010 Jan
PMID:Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants. 2131 64


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