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)

Based on the importance of inflammation in atherogenesis, recent work has focused on whether plasma markers of inflammation can noninvasively diagnose and prognosticate atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherosclerosis, potentially representing attractive therapeutic targets in atherosclerotic disorders, this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect upstream inflammatory activity, stable levels in individuals, and high stability of the actual protein (eg, long half-life and negligible circadian variation) are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (eg, interleukin- 8/CXCL8 and monocyte chemoattractant protein-1/CCL2) have shown to be predictive for future cardiac events in some studies, their role as clinical biomarkers is unclear, and their ability to predict subclinical atherosclerosis has been disappointing. Further prospective studies, including a larger number of patients, are needed to make any firm conclusion. Based on the participation of several chemokines in atherogenesis, it is possible that in the future, combined measurements of multiple chemokines could reveal as a "signature of disease" that can serve as a highly accurate method to assess for the presence of atherosclerotic disease.
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PMID:Chemokines and cardiovascular risk. 1866 88

The epidemiological association between high intakes of n-3 fatty acids (FA) and decreased morbidity and mortality from cardiovascular disease (CVD) can be explained by two main basic mechanisms: (a) an effect on atherothrombosis, and (b) an effect on cardiac arrhythmias. These mechanisms probably reflect different beneficial influences of n-3 FA on cardiovascular biology. Effects on atherothrombosis include the modulation of the expression of pro-atherogenic genes (e.g., endothelial leukocyte adhesion molecules, inflammatory cytokines and cyclooxygenase (COX)-2) and the hepatic synthesis of very low density lipoproteins (VLDL), and are slow in onset, requiring incorporation into cell membrane phospholipids, and usually doses in humans in the order of 3g/day or higher. Effects on cardiac arrhythmias include complex interactions with ion channels (sodium, potassium and calcium channels), typically requiring the presence of free FA in extracellular fluids and usually occurring with lower doses (around 1g/day) of nutritional or pharmacological intake. We have focused most of our research effort in unraveling the pathophysiological background of protection by n-3 FA from atherothrombosis. As the result of incorporation of n-3 FA in the sn-2 position predominantly of the phosphatidyl ethanolamine pool in the inner leaflet of the plasma membrane, n-3 FA appear on the one hand to increase the production of bioactive lipid mediators (protectins and resolvins) affecting cytokine-induced signal transduction; and on the other hand to directly interfere with the generation of reactive oxygen species (mostly hydrogen peroxide), directly responsible for the activation of the transcription factor nuclear factor (NF)-kappaB, which controls the expression of a variety of pro-inflammatory and pro-atherogenic genes, including those encoding for interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)alpha, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and COX-2. The upstream-direct or indirect-inhibition of cytokine- and other atherogenic trigger-induced signaling pathway may involve interference with the activation of protein kinase (PK) C isoforms and NADP(H) oxidase. Such interference may also explain the blunt anti-inflammatory effect of n-3 FA in many experimental models and clinical conditions of inflammation. All together, these mechanisms may provide an integrated view of how n-3 FA may affect CVD.
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PMID:Basic mechanisms behind the effects of n-3 fatty acids on cardiovascular disease. 1895 Oct 2

Chlamydia pneumoniae has during recent years been associated with cardiovascular disease and atherosclerosis. Chemokines, leukocyte adhesion proteins and metalloproteinases are significant for chemotaxis and attachment of leukocytes to vessel walls, and for stability of atherosclerotic plaques. To determine the ability of C. pneumoniae to elicit inflammation in a relevant target host cell, we infected human coronary artery endothelial cells (HCAEC) with a clinical isolate of C. pneumoniae. Extracellular release of five chemokines, two adhesion proteins and a metalloproteinase was measured at different time points after infection using a cytometric bead assay and ELISA. Secretion of IL-8, MCP-1, MIG, IP-10 and ICAM-1 was significantly increased 48 h after C. pneumoniae infection of HCAEC in comparison with uninfected controls. Release of RANTES occurred already 6 h after infection. C. pneumoniae did not elicit release of E-selectin or MMP-1. We conclude that C. pneumoniae induces expression of proinflammatory components in HCAEC, which would promote migration of leukocytes towards endothelial cells. This suggests that C. pneumoniae initiates and propagates vascular inflammation in ways that contribute to coronary artery disease.
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PMID:Expression of chemokines and adhesion molecules in human coronary artery endothelial cells infected with Chlamydia (Chlamydophila) pneumoniae. 1913 11

The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.
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PMID:Obstructive sleep apnea and inflammation. 1924 45

Although cellular senescence and inflammation have been indirectly associated, a direct connection was absent until recently, when two studies proved that senescence at a cellular level is directly linked to an interleukin (IL)-dependent inflammatory network. IL-6 and IL-8, two well-known proinflammatory cytokines, seem to play a central role in premature cellular senescence induction. Activation of the above-mentioned molecules and their receptors is necessary for the initiation of senescence while their deactivation ceases the process. Taking in consideration that atherosclerosis is an inflammatory process and cellular senescence is an emerging cardiovascular risk factor, these new data may be of great importance, especially for chronic kidney disease patients who suffer from increased cardiovascular disease morbidity.
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PMID:Cellular senescence and inflammation: a noteworthy link. 1932 34

Arsenic in drinking water is a major public health concern as it increases risk and incidence of cardiovascular disease and cancer. Arsenic exposure affects multiple vascular beds, promoting liver sinusoidal capillarization and portal hypertension, ischemic heart disease, peripheral vascular disease, and tumor angiogenesis. While Rac1-GTPase and NADPH oxidase activities are essential for arsenic-stimulated endothelial cell signaling for angiogenesis or liver sinusoid capillarization, the mechanism for initiating these effects is unknown. We found that arsenic-stimulated cell signaling and angiogenic gene expression in human microvascular endothelial cells were Pertussis toxin sensitive, indicating a G-protein coupled signaling pathway. Incubating human microvascular endothelial cells with the sphingosine-1-phosphate type 1 receptor (S1P(1)) inhibitor VPC23019 or performing small interfering RNA knockdown of S1P(1) blocked arsenic-stimulated HMVEC angiogenic gene expression and tube formation, but did not affect induction of either HMOX1 or IL8. Liver sinusoidal endothelial cells (LSECs) defenestrate and capillarize in response to aging and environmental oxidant stresses. We found that S1P(1) was enriched on LSECs in vivo and in primary cell culture and that VPC23019 inhibited both sphingosine-1-phosphate-stimulated and arsenic-stimulated LSEC oxidant generation and defenestration. These studies identified novel roles for S1P(1) in mediating arsenic stimulation of both angiogenesis and pathogenic LSEC capillarization, as well as demonstrating a role for S1P(1) in mediating environmental responses in the liver vasculature, providing possible mechanistic insight into arsenic-induced vascular pathogenesis and disease.
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PMID:Arsenic requires sphingosine-1-phosphate type 1 receptors to induce angiogenic genes and endothelial cell remodeling. 1934 68

Interleukin-8 is a strong mediator of inflammation and has been implicated in the biochemical pathways involved in a wide range of inflammatory diseases including atherosclerosis. We investigated the potential influence of two common functional polymorphisms of the interleukin (IL)-8 gene: -251A/T and 781C/T on susceptibility to in stent restenosis (ISR) following percutaneous coronary intervention (PCI). The hypothesis was tested by screening for the prevalence of the above polymorphisms in 201 coronary artery disease (CAD) patients subjected to PCI and presenting with symptoms or signs of recurrent ischemia. Patients were angiographically re-evaluated and formed the ISR group (n = 73) and the non-ISR group (n = 128) based on the presence or absence of ISR. One hundred and forty-seven subjects without angiographic evidence of CAD formed a reference control group (non-CAD group). A borderline statistically significant higher frequency of the TT(251)TT(781) combined genotype was observed in patients with ISR on re-evaluation compared with patients with normal follow-up angiography. The predominance of TT(251)TT(781) was independent of conventional risk factors for cardiovascular disease. Consequently, T(251)T(781) haplotype was significantly more common in the ISR group. The above observations indicate that the genetic diversity of the IL-8 gene influences patient susceptibility to ISR and suggests the implication of IL-8-mediated pathways in the process of ISR. However, the rarity of T(251)T(781) haplotype makes any clinical application of the above observations unfeasible.
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PMID:Interleukin 8 gene polymorphisms and susceptibility to restenosis after percutaneous coronary intervention. 1940 19

Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disease and is recognised as a major public health burden. Large-scale epidemiological studies have demonstrated an independent relationship between OSAS and various cardiovascular disorders. The pathogenesis of cardiovascular complications in OSAS is not completely understood but a multifactorial aetiology is likely. Inflammatory processes have emerged as critical in the pathogenesis of atherosclerosis at all stages of atheroma formation. Increased levels of various circulating markers of inflammation including tumour necrosis factor alpha (TNFalpha), interleukin 6 (IL6), IL-8 and C-reactive protein (CRP) have been reported as associated with future cardiovascular risk. There is increasing evidence of elevated inflammatory markers in OSAS with a significant fall after effective treatment with continuous positive airway pressure. This evidence is particularly strong for TNFalpha, whereas studies on IL6 and CRP have yielded conflicting results possibly due to the confounding effects of obesity. Cell culture and animal studies have significantly contributed to our understanding of the underlying mechanisms of the association between OSAS and inflammation. Intermittent hypoxia, the hallmark of OSAS, results in activation of pro-inflammatory transcription factors such as nuclear factor kappa B (NF-kappaB) and activator protein (AP)-1. These promote activation of various inflammatory cells, particularly lymphocytes and monocytes, with the downstream consequence of expression of pro-inflammatory mediators that may lead to endothelial dysfunction. This review provides a critical analysis of the current evidence for an association between OSAS, inflammation and cardiovascular disease, discusses basic mechanisms that may be responsible for this association and proposes future research possibilities.
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PMID:Systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? 1956 Dec 83

Since the establishment of the inflammatory basis of atherosclerosis, several pro- or anti-inflammatory agents have been examined as potential mediators of the biochemical pathways of lesion formation. Interleukin (IL)-8 was first characterized in 1987. Since then, knowledge regarding its role in leucocyte trafficking and activation has advanced rapidly, especially in the field of cardiovascular disease. In the scientific literature, there is sufficient evidence to support beyond any doubt the involvement of IL-8 in the establishment and preservation of the inflammatory micro-environment of the insulted vascular wall. However, how the information derived from in vitro studies and animal models can be applied in clinical practice has yet to be determined. In the present review, the available evidence regarding the role of IL-8 in cardiovascular disease is presented, and future perspectives are discussed.
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PMID:Interleukin 8 and cardiovascular disease. 1961

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome represent two of the most prevalent chronic respiratory disorders in clinical practice, and cardiovascular diseases represent a major comorbidity in each disorder. The two disorders coexist (overlap syndrome) in approximately 1% of adults but asymptomatic lower airway obstruction together with sleep-disordered breathing is more prevalent. Although obstructive sleep apnea syndrome has similar prevalence in COPD as the general population, and vice versa, factors such as body mass index and smoking influence relationships. Nocturnal oxygen desaturation develops in COPD, independent of apnea/hypopnea, and is more severe in the overlap syndrome, thus predisposing to pulmonary hypertension. Furthermore, upper airway flow limitation contributes to nocturnal desaturation in COPD without apnea/hypopnea. Evidence of systemic inflammation in COPD and sleep apnea, involving C-reactive protein and IL-6, in addition to nuclear factor-kappaB-dependent pathways involving tumor necrosis factor-alpha and IL-8, provides insight into potential basic interactions between both disorders. Furthermore, oxidative stress develops in each disorder, in addition to activation and/or dysfunction of circulating leukocytes. These findings are clinically relevant because systemic inflammation may contribute to the pathogenesis of cardiovascular diseases and the cell/molecular pathways involved are similar to those identified in COPD and sleep apnea. However, the pathophysiological and clinical significance of systemic inflammation in COPD and sleep apnea is not proven, and thus, studies of patients with the overlap syndrome should provide insight into the mechanisms of systemic inflammation in COPD and sleep apnea, in addition to potential relationships with cardiovascular disease.
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PMID:Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. 1962 78


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