Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obstructive sleep apnea (OSA), a breathing disorder in sleep characterized by intermittent hypoxia and sleep fragmentation, constitutes an independent risk factor for cardiovascular morbidity. Investigating how this breathing disorder modulates immune responses may facilitate understanding one of the risk factors for atherosclerosis. T cells play a significant role in atherogenesis and plaque development via cytokine production and by directly contributing to vascular injury. Using flow cytometry and chromium release assays, we found that CD4 and CD8 T cells of OSA patients undergo phenotypic and functional changes and acquire cytotoxic capabilities. Thus, a shift in CD4 and CD8 T cells toward type 2 cytokine dominance with increased IL-4 expression was noted. IL-10 expression in T cells was negatively correlated with the severity of OSA, as determined by the apnea-hypopnea index (AHI), whereas TNF-alpha was positively correlated. CD8 T cells of OSA patients expressed a fourfold increase in TNF-alpha and CD40 ligand (CD40L), and exhibited an increased OSA severity-dependent cytotoxicity against endothelial cells. The percentage of CD4(+)CD28(null) and cytotoxicity of CD4 T lymphocytes were also significantly higher in OSA patients than in controls. Nasal continuous positive airway pressure (nCPAP) treatment, which ameliorated the severity of OSA, significantly lowered TNF-alpha and CD40L expression, and decreased cytotoxicity in CD8 T cells. In conclusion, increased cytotoxicity and cytokine imbalance in CD4 and CD8 T cells may be involved in atherogenesis in OSA. Nasal CPAP treatment ameliorates some lymphocyte dysfunctions and thus may moderate some atherogenic pathways.
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PMID:Lymphocyte activation as a possible measure of atherosclerotic risk in patients with sleep apnea. 1612 76

Chronic inflammation is one of the main underlying mechanisms in the development of coronary artery disease (CAD). We investigated the prognostic value of inflammatory markers for cardiac events occurring more than 6 months after percutaneous coronary intervention (PCI), i.e. late cardiac events, furthermore we investigated the temporal stability of these markers. Exhausted patients (234) recently treated by successful PCI were studied. Serum samples collected about 6 weeks after PCI (baseline), 6 and 18 months after baseline were analyzed for CRP, IL-6, tumour necrosis factor (TNF-alpha), IL-10, IL-1ra, IL-8 and neopterin. In the mean cardiac follow-up of 24 months, 25 late cardiac events occurred. Cox proportional hazards analysis was used to determine the prognostic value. Elevated concentrations of IL-6 at baseline and 6 months later increased the risk of late cardiac events (RR 3.9, CI 1.7-9.0, p 0.00 and RR 3.6, CI 1.6-8.5, p 0.00). Elevated concentrations of CRP and IL-10 at baseline also increased the risk of late cardiac events (RR 2.5, CI 1.1-5.7, p 0.04 and RR 2.5, CI 1.1-5.6, p 0.03) as did IL-1 receptor antagonist at 6 months (RR 2.6, CI 1.1-6.1, p 0.04). Temporal stability was high for most markers, but highest for IL-6. These results support the assumption that chronic inflammation is a pathophysiological mechanism in the development of CAD.
Atherosclerosis 2005 Oct
PMID:Inflammatory markers predict late cardiac events in patients who are exhausted after percutaneous coronary intervention. 1615 7

Insulin resistance has been implicated as one possible factor that links visceral obesity to unfavourable metabolic and cardiovascular consequences. However, the mechanism whereby adipose tissue causes alterations in insulin action remains unclear. White adipose tissue is secreting several hormones, particularly leptin and adiponectin, and a variety of other protein signals: the adipocytokines. They include proteins involved in the regulation of energy balance, lipid and glucose metabolism as well as angiogenesis, vascular and blood pressure regulation. Visceral obesity and inflammation within white adipose tissue may be a crucial step contributing to the emergence of insulin resistance, type 2 diabetes and atherosclerosis. A growing list of adipocytokines involved in inflammation (IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, TGF-beta,) and the acute-phase response (serum amyloid A, PAI-1) have been found to be increased in the metabolic syndrome. It is, however, unclear as to the extent adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and how they may affect the insulin-dependent tissues. This review describes the role of the currently known adipocytokines and hormones released by adipose tissue in generating the insulin resistance state and the chronic inflammatory profile which frequently goes together with visceral obesity.
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PMID:Review article: adipocytokines and insulin resistance. 1622 63

Apolipoprotein A-I (apoA-I), the major protein component of serum high-density lipoprotein, exhibits anti-inflammatory activity in atherosclerosis. In this study, we demonstrate that apoA-I inhibits DC differentiation and maturation. DC differentiated from monocytes in the presence of apoA-I showed a decreased expression of surface molecules such as CD1a, CD80, CD86, and HLA-DR. In addition, these DC exhibited decreased endocytic activity and weakened allogeneic T-cell activation. During DC differentiation in the presence of apoA-I, PGE(2) and IL-10, which are known to be DC differentiation inhibitors and/or modulators of DC function, were produced at remarkable rates, whereas IL-12 production in the cells after stimulation with CD40 mAb and IFN-gamma was significantly decreased in comparison with the control DC. T cells stimulated by apoA-I-pretreated DC produced significantly low levels of IFN-gamma, and apoA-I inhibited cross-talk between DC and NK cells, in terms of IL-12 and IFN-gamma production. Therefore, apoA-I appears to play an important role in modulating both innate immune response and inflammatory response. The novel inhibitory function of apoA-I on DC differentiation and function may facilitate the development of new therapeutic interventions in inflammatory diseases.
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PMID:Apolipoprotein A-I induces IL-10 and PGE2 production in human monocytes and inhibits dendritic cell differentiation and maturation. 1625 56

Macrophage apoptosis and the ability of phagocytes to clear these apoptotic cells are important processes in advanced atherosclerosis. Phagocytic clearance not only disposes of dead cells but usually elicits an anti-inflammatory response. To study this process in a model of advanced lesional macrophage death, macrophages rendered apoptotic by free cholesterol loading (FC-AMs) were incubated briefly with fresh macrophages ("phagocytes"). FC-AMs were promptly ingested by the phagocytes, which was dependent upon actin polymerization and the phagocyte Mer receptor. Surprisingly, this brief exposure to FC-AMs triggered a modest proinflammatory response in the phagocytes: tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta were induced, whereas the levels of transforming growth factor-beta and IL-10 were not increased. This response required cell contact between the FC-AMs and phagocytes but not FC-AM ingestion. TNF-alpha and IL-1beta induction required one or more proteins on the FC-AM surface and was dependent on signaling through extracellular signal-regulated kinase-1/2 mitogen-activated protein kinase and nuclear factor-kappaB in the phagocytes. TNF-alpha production was markedly greater when Mer-defective phagocytes were used, indicating that Mer attenuated the inflammatory response. Interestingly, a more typical anti-inflammatory response was elicited when phagocytes were exposed to macrophages rendered apoptotic by oxidized low density lipoprotein or UV radiation. Thus, the proinflammatory milieu of advanced atherosclerotic lesions may be promoted, or at least not dampened, by contact between FC-induced apoptotic macrophages and neighboring phagocytes prior to apoptotic cell ingestion.
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PMID:Cholesterol-induced apoptotic macrophages elicit an inflammatory response in phagocytes, which is partially attenuated by the Mer receptor. 1638 Mar 74

Nuclear factor-kappa B (NF-kappaB) is a transcription factor that resides in the cytoplasm of every cell and translocates to the nucleus when activated. Its activation is induced by a wide variety of agents including stress, cigarette smoke, viruses, bacteria, inflammatory stimuli, cytokines, free radicals, carcinogens, tumor promoters, and endotoxins. On activation, NF-kappaB regulates the expression of almost 400 different genes, which include enzymes (e.g., COX-2, 5-LOX, and iNOS), cytokines (such as TNF, IL-1, IL-6, IL-8, and chemokines), adhesion molecules, cell cycle regulatory molecules, viral proteins, and angiogenic factors. The constitutive activation of NF-kappaB has been linked with a wide variety of human diseases, including asthma, atherosclerosis, AIDS, rheumatoid arthritis, diabetes, osteoporosis, Alzheimer's disease, and cancer. Several agents are known to suppress NF-kappaB activation, including Th2 cytokines (IL-4, IL-13, and IL-10), interferons, endocrine hormones (LH, HCG, MSH, and GH), phytochemicals, corticosteroids, and immunosuppressive agents. Because of the strong link of NF-kappaB with different stress signals, it has been called a "smoke-sensor" of the body.
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PMID:Transcription factor NF-kappaB: a sensor for smoke and stress signals. 1638 90

Cardiovascular diseases (CVD), such as myocardial infarction (MI), are major causes of disability and mortality in the elderly. The increasing burden of CVD in ageing industrialized populations requires intensive research in order to improve preventive and therapeutic strategies especially in old people and if possible slow the processes of cardiovascular disease generation and progression. Ageing is accompanied by an age-dependent up-regulation of the inflammatory response, due to chronic antigenic stress stimulation, which potentially triggers the onset of inflammatory diseases, especially CVD. However, the exact mechanisms are still poorly understood. Since CVD are caused by interactions between genetic and environmental factors, a possible approach to their prevention is to identify the potential genetic component of inflammatory cardiovascular risk factors, providing the basis for personalized lifestyle modification and improved pharmacological therapy. Some common gene polymorphisms associated with high production of inflammatory molecules have been associated with atherosclerosis. Therefore, controlling inflammation might play a protective role against CVD, especially in ageing. Although a large number of studies of pro- and anti-inflammatory gene variants in association with CVD and MI exists, the emerging data are quite conflicting and do not provide definitive evidence for a role of these polymorphisms in the pathogenesis of MI. In this paper we review the evidence for a possible role of genetic polymorphisms of the most important inflammatory cytokines (IL-6, TNF-alpha, IL-10) and immune receptors (CD14 receptor and TLR-4) in modulating the incidence or the prognosis of MI, with a special focus in ageing population.
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PMID:Genetic polymorphisms of inflammatory cytokines and myocardial infarction in the elderly. 1651 51

Some cytokines have been involved in the pathogenesis of late onset Alzheimer's disease (LOAD). A possible increase in plasma cytokines levels has been reported in LOAD and vascular dementia (VD), but the results of previous studies are conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL-10 in four groups of older individuals: 60 patients with LOAD, 80 patients with VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42 controls (C). By analysis of covariance (adjustment for age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By logistic regression analysis, we demonstrated that high levels (defined as above the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with increased likelihood of having VD and LOAD compared to C, while high IL-6 levels were associated with a increased probability of having VD, compared with LOAD. Our study support the notion of a low-grade systemic inflammation in older patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF-alpha levels. The high IL-6 levels found in VD might be not a specific finding, as it might come from several conditions including atherosclerosis and related vascular risk factors, comorbidity, and frailty.
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PMID:Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. 1660 Feb 99

IL-20 belongs to the IL-10 family and plays a role in skin inflammation and the development of hematopoietic cells. Little is known about its other biological functions and clinical implications, however. Updated information about IL-20, such as its identification, expression, receptors, signaling, biological activities, and potential clinical implications, is illustrated in this review based on our research and on data available in the literature. Our studies of IL-20 show that it is a pleiotropic cytokine with potent inflammatory, angiogenic, and chemoattractive characteristics. Inflammation and angiogenesis are essential for the pathogenesis of rheumatoid arthritis and atherosclerosis. Based on in vitro data and clinical samples, we demonstrated that IL-20 is involved in the diseases of rheumatoid arthritis and atherosclerosis. In addition, we found in our studies that IL-20 signaled through different molecules in several cells. The present review presents the clinical implications of IL-20 in rheumatoid arthritis and atherosclerosis. It may provide new therapeutic options in the future.
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PMID:IL-20: biological functions and clinical implications. 1670 17

Some studies have shown correlations between selected proinflammatory factors and carotid atherosclerosis. It has not been established whether anti-inflammatory cytokines are associated with carotid intima-media thickness (IMT), an ultrasound surrogate marker of atherosclerosis. Therefore, the authors studied the relationship between the carotid IMT and serum levels of interleukin (IL)-10 and transforming growth factor-beta1 in 76 subjects. They discovered that lower IL-10 levels were associated with increased mean IMT in common carotid arteries.
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PMID:Anti-inflammatory cytokines in subclinical carotid atherosclerosis. 1680 69


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