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)

Recent studies provide evidence that infectious agents play a causal role in the pathogenesis of atherosclerosis. In this respect, a chronic persistent Chlamydia pneumoniae infection, indicated by the presence of chlamydial heat shock protein 60 (cHSP 60), is of central interest. Both cHSP60 and endogenous human (h) HSP60 are upregulated under stress conditions in intimal cells and serve as a target for cross-reactive cytotoxic HSP-serum-antibodies. Therefore, the present study evaluates the expressions of both HSP60 homologues in advanced human coronary lesions and a correlation between intimal tissuebound protein and serum antibodies (Ab) to HSP65. Coronary atherectomy specimens retrieved from 114 primary target lesions of patients with acute coronary syndrome (ACS; n=46) or stable angina (SA; n=68) were assessed immunohistochemically for the presence of cHSP60 and hHSP60. Chronic persistency of Chlamydia pneumoniae was additionally examined by transmission electron microscopy. Blood samples from30 patients were tested for anti-Chlamydia pneumoniae-IgG/IgA- and anti-HSP65-Ab titers and for serum CRP levels. Coronary plaques revealed immunoreactive cHSP60 in 47% and hHSP60 in 57% of the lesions colocalized within macrophages/foam cells. Chlamydia in foam cells most often presented ultrastructural patterns that pointed to the persistency of the pathogen. Intact, non-atherosclerotic vessels showed no signals. Mean expressions were 3.1% for cHSP60 and 3.3% for hHSP60. As a central finding, the expression of both HSP homologues was significantly (each p<0.001) higher in ACS lesions compared to SA lesions (cHSP60: 6.2 vs 1.0%, and hHSP60: 7.2 vs 0.7%). Moreover, we found positive correlations between both determinants in ACS and SA lesions (r=0.41, r=0.37; p<0.01). Most interestingly, cHSP60 revealed no relationship with anti-Chlamydia pneumoniae-IgG/IgA titers, whereas expression of cHSP60 as well as that of hHSP60 correlated with anti-HSP65-Ab titers (r=0.50, p<0.01, and r=0.42, p<0.05, respectively).cHSP60 and hHSP60 colocalize within coronary primary atheroma, most prevalent in lesions associated with ACS. For the first time, our data demonstrate a significant correlation between the intimal expression of these HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions to bacterial and human HSPs may play an important role in coronary atherosclerosis and plaque instability.
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PMID:[Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link between infection and atherosclerosis]. 1281 94

The observation that systemic inflammatory rheumatic diseases such as rheumatoid arthritis (RA) are associated with a significantly increased rate of cardiovascular disease, which often occurs at a younger age than in the normal population, is particularly important given the increasing interest in the role of inflammation in atherogenesis in the general population. This review examines the accumulating evidence for accelerated atherogenesis of RA and updates the hypothesis that vasculitis plays a major role in this. Endothelial dysfunction (ECD), widely regarded as initial lesion in atherogenesis, has been shown to occur commonly in primary vasculitis. This ECD is a diffuse event, demonstrable in more than one vascular bed. It is not simply due to scarring in the vessel wall, related to the focal inflammation of the underlying vasculitis, since it may be reversed by suppression of the immune inflammation. However, the mechanisms for this ECD differ from that of the primary vasculitis. Preliminary evidence suggests that inflammatory mediators such as CRP, TNF, or sphingolipids may be involved. The diffuse ECD of vasculitis may have important consequences for both the progression of the primary disease and for cardiovascular events. A model for the role of vasculitis-induced ECD in the accelerated atherogenesis of rheumatic diseases is presented. These concepts are discussed together with the messages they suggest for 'idiopathic' atherosclerosis in the general population.
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PMID:Accelerated atherogenesis in autoimmune rheumatic diseases. 1284 89

Associations between hemostatic and inflammatory markers relative to the ankle brachial index (ABI), an indicator of the presence and severity of peripheral arterial disease (PAD), are not fully understood. We studied relations among selected hemostatic factors, inflammatory markers, and the ankle brachial index (ABI) in patients with and without peripheral arterial disease (PAD). Participants were 370 men and women with ABI <0.90 and 231 patients with ABI 0.90 to 1.50 identified from noninvasive vascular laboratories and general medicine practice. Blood factors were D-dimer, prothrombin 1.2, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), and inflammatory markers (high-sensitivity C-reactive protein [CRP], fibrinogen, and serum amyloid A [SAA]). Among patients without a history of cardiac or cerebrovascular disease, the ABI was significantly inversely associated with log D-dimer (p <0.001), log prothrombin 1.2 (p = 0.001), log CRP (p <0.001), and log fibrinogen (p = 0.005) in unadjusted analyses. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, D-dimer was associated independently with ABI in participants with a history of cardiac or cerebrovascular disease (p = 0.003) and in participants without a history of cardiac or cerebrovascular disease (p = 0.017). In these analyses, CRP was associated independently with ABI among participants with a history of cardiac or cerebrovascular disease (p = 0.026). CRP was not associated independently with ABI in participants without a history of cardiac or cerebrovascular disease. We conclude that D-dimer levels may be more sensitive than other blood markers for measuring the extent of atherosclerosis in lower extremity arteries.
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PMID:Relation of levels of hemostatic factors and inflammatory markers to the ankle brachial index. 1286 Feb 23

Statins, aspirin and angiotensin II modulators (A II-M: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type I receptor blockades) may have an anti-inflammatory effect, but the relationship between the effects of statins, aspirin and A II-M on high-sensitive C-reactive protein (hs-CRP) levels remains to be determined. We examined serum hs-CRP levels in consecutive patients with stable ischemic heart disease (IHD) (n=1231; 65+/-9 years; male/female, 927/304) and without IHD (n=226; 64+/-9 years; male/female, 117/109). Blood samples were collected on the day of catheterization. The hs-CRP levels were significantly higher in the IHD than in the non-IHD patients (0.32+/-0.52 vs. 0.24+/-0.29 mg/dl, P<0.05). Treatment with statins was associated with significantly lower hs-CRP levels in both groups (non-IHD, 0.17+/-0.14 vs. 0.26+/-0.31 mg/dl; IHD, 0.27+/-0.34 vs. 0.35+/-0.59 mg/dl; both P<0.05). hs-CRP levels were significantly lower only in IHD patients treated with A II-M than in those not treated with A II-M (0.28+/-0.34 vs. 0.34+/-0.58 mg/dl, P<0.05). Aspirin did not have any effect on the hs-CRP level in either group. The hs-CRP levels were significantly lower in IHD patients treated with statins and/or A II-M than those treated with neither statins nor A II-M (statin+/A II-M+, 0.28+/-0.29 mg/dl; statin+/A II-M-, 0.26+/-0.36 mg/dl; statin-/A II-M+, 0.28+/-0.37 mg/dl; statin-/A II-M-, 0.38+/-0.66 mg/dl; P<0.01). These results indicate that statins and A II-M, but not aspirin, in commonly used doses have an anti-inflammatory action as assessed by measurement of CRP levels in IHD patients.
Atherosclerosis 2003 Jul
PMID:Relationship between effects of statins, aspirin and angiotensin II modulators on high-sensitive C-reactive protein levels. 1286 Feb 62

Insulin resistance has been recognized as an inflammatory disease based on the scientific evidence collected over the last decade. Inflammatory markers like CRP, PAI-1, IL-6 are present in higher concentrations in insulin resistant people than in normal people. Mechanisms, linking inflammation to insulin resistance are being explored and progress has been made in this direction. TNFalpha has been shown to be responsible for insulin resistance in obese subjects. Macronutrient intake may also induce inflammation whereas fasting has anti-inflammatory effects. Insulin itself has been found to be anti-inflammatory and this action may be useful in many disease states. Thiazolidinediones, such as rosiglitazone that act primarily as insulin sensitisers, have a profound anti-inflammatory and potentially antiatherosclerotic activity. These effects may be of considerable clinical significance if sustained during long-term therapy, given the morbidity and mortality associated with atherosclerosis, the major complication of insulin resistance.
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PMID:Insulin resistance as a proinflammatory state: mechanisms, mediators, and therapeutic interventions. 1286 63

The possible role of inflammation in coronary artery disease (CAD) is being recognised, while markers of inflammation (e.g., CRP) and infection with Chlamydia pneumoniae (C. pneumoniae), cytomegalovirus (CMV) and Helicobacter pylori (H. pylori) have been proposed as risk factors for CAD. However, these associations require further evaluation. It is a known fact that diabetic patients suffer from impaired immune response to some pathogens and a high incidence of atherosclerosis. In this case-control study we investigated serological markers of infection with C. pneumoniae, CMV, and H. pylori in a group of 140 patients with unstable angina pectoris (UA), 52 of them having type 2 diabetes mellitus, and in a matched control group. Anamnestic (IgG) and acute infection (IgA) antibodies against the above agents were tested using ELISA or indirect immunofluorescence tests. In patients with UA we found a significantly higher seroprevalence and titres of IgG antibodies against C. pneumoniae (p = 0.04) and increased titres of IgG antibodies against CMV (p = 0.007). No differences were found in IgA antibody response to these pathogens. Antibody response to H. pylori was similar in both groups tested. In diabetic patients with UA, the frequency of group-common IgG antibodies against C. pneumoniae was higher than in the non-diabetic UA patients. The other serological markers studied were comparable in the patients with or without diabetes mellitus. Our findings confirmed association of C. pneumoniae and CMV with cardiovascular heart disease. Moreover, diabetes mellitus may predispose the patients to C. pneumoniae infection. However, serological markers observed do not indicate that destabilisation of angina pectoris is associated with acute C. pneumoniae or CMV infection. No relationship was found between UA and H. pylori infection.
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PMID:Serological markers of Chlamydia pneumoniae, cytomegalovirus and Helicobacter pylori infection in diabetic and non-diabetic patients with unstable angina pectoris. 1288 57

Atherosclerosis is nowadays generally accepted as an inflammatory disease. It is known that local inflammation occurs in the formation the plaques, as macrophages and other immuno-competent cells are present in the lesions from an early stage, and it is also known that inflammation plays an important role in the weakening of the fibrous cap of the advanced plaque, eventually leading to plaque rupture and acute coronary syndromes. The present review focuses on two questions. First, if circulating markers of inflammation could differentiate between healthy subjects and those with atherosclerotic manifestations. Second, if those markers could differentiate between those with a stable atherosclerotic disease, such as stable angina pectoris, and those prone to unstable manifestations of atherosclerosis, such as acute coronary syndromes. Using data from both cross-sectional and prospective studies it could be shown that the majority of the studies which had investigated the role of markers for systemic inflammation, such as CRP, leukocyte count, serum fibrinogen and different cytokines, found elevated levels in patients with atherosclerosis and especially so in those with an unstable coronary disease. The same pattern was found when inflammatory markers with a vascular origin, such as the adhesion molecules, were investigated. Thus, based on the literature it is obvious that circulating markers of inflammation have a role as risk factors for unstable manifestations of atherosclerosis, but it is still unclear whether the different inflammatory markers merely are markers, or if they in an active way contribute to the development and progression of the atherosclerotic disease in their own.
Atherosclerosis 2003 Aug
PMID:Circulating markers of inflammation and atherosclerosis. 1292 71

Insulin resistance (IR)/hyperinsulinemia and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP]) can predict cardiovascular disease. However, because IR and inflammation (IF) have not been evaluated simultaneously, it is not known whether IR and IF are independently related to cardiovascular disease. Furthermore, the combined effect of IR and IF on the prediction of cardiovascular disease is presently unknown. Thus, we measured insulin sensitivity (K index of the insulin tolerance test; KITT) and hs-CRP in 350 Japanese patients with type 2 diabetes, and followed them for 1-7 years (mean, 4.5 years). During the follow-up, 33 patients died and 53 patients developed non-fatal coronary artery disease or stroke (endpoint). Age, systolic blood pressure, current smoking, past history of cardiovascular disease, KITT, and hs-CRP independently and significantly correlated with endpoint. One-S.D. difference was associated with a significant increase of relative risk in KITT (1.45; 95% CI 1.09-1.91) and hs-CRP (1.30; 1.04-1.67). When patients were subdivided to tertile, the relative risk in the highest tertile of KITT was 1.76 (95% CI 1.01-3.11) and hs-CRP was 2.00 (1.03-3.85) compared with the patients with lowest tertile. The relative risk in the highest tertile of both KITT and hs-CRP was 5.32 (1.18-24.0) compared with the lowest tertile of both values. In conclusion, low-grade IF and IR are independently related to all-cause of death and cardiovascular disease in Japanese patients with type 2 diabetes. Coexistence of low-grade IF and IR amplify this effect.
Atherosclerosis 2003 Aug
PMID:Inflammation and insulin resistance are independently related to all-cause of death and cardiovascular events in Japanese patients with type 2 diabetes mellitus. 1292 84

Hypercholesterolemia causes endothelial dysfunction, an early feature of atherosclerosis, leading to increased production of adhesion molecules and cytokines. The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules, interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in patients with non-familial hypercholesterolemia. Fifty-five patients with non-familial hypercholesterolemia were randomized to treatment with atorvastatin 10 mg/day or placebo for 3 months. Soluble intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium. There was a significant reduction in ICAM-1 at 2 weeks (p<0.0001) with further reduction at 3 months (p<0.0001). At 3 months, there were significant reductions in VCAM-1 (p<0.02), IL-6 (p<0.0001) and hs-CRP (p<0.01), but an increase in E-selectin levels (p<0.002). Treatment with statin was an independent determinant of change in ICAM-1 (p<0.05) and IL-6 levels (p<0.05) after correcting for anthropometric indices, blood pressure and lipid profile. Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function, suggesting an attenuation of endothelial activation and improvement in endothelial function, independent of lipid lowering. This may lead to a reduction in the progression of atherosclerosis.
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PMID:Reduction in serum levels of adhesion molecules, interleukin-6 and C-reactive protein following short-term low-dose atorvastatin treatment in patients with non-familial hypercholesterolemia. 1295 65

Infection with Chlamydia pneumoniae has been suggested to play a role in the development and maintenance of atherosclerosis based on differences in the prevalence of antibodies against Chlamydia pneumoniae in patients with and without atherosclerotic lesions. We evaluated the prevalence of Chlamydia pneumoniae DNA in the white cells of the peripheral blood in 194 patients with diabetes mellitus, 50 patients with acute coronary syndrome, 102 hypertensive patients, 193 patients having suffered a stroke and in 368 healthy subjects with a nested polymerase chain reaction (nPCR). Overall the prevalence of Chlamydia pneumoniae DNA in peripheral blood cells was: diabetes mellitus (11.9%), stroke (10.4%), hypertension (6.9%), acute coronary syndrome (4.0%) and healthy subjects (7.9%). The prevalence of Chlamydia pneumoniae DNA in the patients was not significantly different from prevalence in the healthy subjects. However, a significant association was found between high levels of triglycerides and presence of C. pneumoniae DNA (OR = 3.27, p < 0.04). The prevalence of C. pneumoniae DNA was not associated with age, gender, smoking, BMI, HDL, CRP, plasma creatinine and symptoms or signs of ischaemic heart disease. The association between high levels of triglycerides and C. pneumoniae DNA suggests that infection by C. pneumoniae affects lipid metabolism.
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PMID:Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in healthy control subjects and patients with diabetes mellitus, acute coronary syndrome, stroke, and arterial hypertension. 1460 8


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