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)

Chlamydia pneumoniae infection implicated as an important etiologic factor of atherosclerosis, especially in coronary artery disease (CAD), was found in vitro to be associated with the induction of matrix metalloproteinases (MMPs). An extracellular matrix metalloproteinase inducer (EMMPRIN)/ membrane-type 1 matrix metalloproteinase (MT1-MMP) system which induces and activates MMPs, is suggested to be functional and were upregulated in the failing myocardium. However, the upstream regulation of MMPs by C. pneumoniae within atheroma itself remains unclear. We evaluated the seroepidemiologic study of C. pneumoniae infection in CAD patients (n= 391) and controls (n=97) and performed histopathological and in vitro analysis in atherosclerotic vascular tissues obtained from patients with seropositive to C. pneumoniae (n=20), by using immunochemistry for C. pneumoniae, EMMPRIN/MT1-MMP, MMP-2, and MMP-9. The seropositive rates of both anti-C. pneumoniae IgG and IgA were 56.7% in CAD group and 43.3% in control group (P=0.033). Seropositive rate was increased in subgroups of CAD patients without conventional coronary risk factors compared to those with conventional risk factors. Immunoreactivities of EMMPRIN, MT1-MMP, MMP-2, and MMP-9 were increased in the atheromatous plaque itself, predominantly in immunoreactive macrophages/mononuclear cells to C. pneumoniae. Furthermore, Western blot analysis showed that EMMPRIN and MMP-2 were detected more prominently in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. Zymographic analysis revealed that activities of MMP-2 and MMP-9 were more increased in atherosclerotic tissues infected with C. pneumoniae compared to control tissues. The present study demonstrated upstream regulation of MMPs can be induced by C. pneumoniae within atheromatous plaque itself. These findings help to understand the potential role of C. pneumoniae in the progression of atherosclerosis.
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PMID:Upregulation of extracellular matrix metalloproteinase inducer (EMMPRIN) and gelatinases in human atherosclerosis infected with Chlamydia pneumoniae: the potential role of Chlamydia pneumoniae infection in the progression of atherosclerosis. 1252 80

In non-atheromatous segments of coronary arteries a sequence of preatherosclerotic changes was identified which consisted of medial thickening followed by intimal thickening. More recently, Chlamydia pneumoniae seropositivity was associated with enhanced intima-media thickness of arteries. In the present study the intimal and medial thickness of coronary artery of young adults were measured, and were correlated with the presence of Chlamydia pneumoniae antigens. Proximal and distal segments of the left anterior descending coronaries (LAD) obtained at autopsy from young adults (15-34 years) were studied. The thickness and cellular density of the intima and of the media without clear-cut atherosclerotic changes were measured by image analysis. The hypertrophy index was calculated as the ratio of cell density and the thickness of the respective layer. Atherosclerotic lesions occurring elsewhere in the same coronary were noted and graded by severity. The presence of Chlamydia pneumoniae verified by immunohistochemistry was correlated with the severity of lesions and with the hypertrophy index. In the proximal segments, atherosclerosis of LAD was associated with the widening of both the intima and the media of lesion free-sites. In the distal coronary segments the proportion of the intimal thickening had a significant association with atherosclerosis. Compared to non-infected arteries, Chlamydia pneumoniae infection was associated with higher hypertrophy index in the intima as well as in the media. The rate of Chlamydia pneumoniae positivity increased with the severity of lesions. As a conclusion: in the LAD coronary, the intimal thickening is the main preatherosclerotic change. Chlamydia pneumoniae may favour arterial wall hypertrophy and plays a role in lesion progression.
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PMID:Early atherosclerosis and Chlamydia pneumoniae infection in the coronary arteries. 1270 46

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

Recent studies have suggested that Chlamydia pneumoniae infection is an important factor in the development of atherosclerosis. The C(-260)-->T polymorphism in the CD14 promoter gene has been reported to regulate the density of CD14 expression on monocytes for the activation of monocytes to secrete inflammatory cytokines by lipopolysaccharide. We investigated this genetic marker and its association with C. pneumoniae infection. Among 315 healthy subjects, the distribution of the C(-260)-->T polymorphism in the CD14 promoter gene was 14.9% for the CC genotype, 54.3% for the CT genotype, and 30.8% for the TT genotype. Among subjects with the 3 CD14 genotypes, 59.5%, 64.9%, and 78.3%, respectively, were seropositive for C. pneumoniae. With multiple logistic regression analysis, the odds ratio of C. pneumoniae infection was 2.08 for CD14 TT genotype (95% confidence interval, 1.18-3.69; P=.016). A significant association between the CD14 TT genotype and C. pneumoniae infection was found.
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PMID:Association of CD14 promoter gene polymorphism and Chlamydia pneumoniae infection. 1282 76

Atherosclerosis has been linked to Chlamydia pneumoniae infection. In atherosclerotic arteries chlamydiae infect macrophages, endothelial cells, and smooth muscle cells (SMC). It has been suggested that the proteolysis of the extracellular matrix by matrix metalloproteinases (MMPs) is involved in the destabilisation and rupture of atherosclerotic plaques. In this study we investigated the expression of several MMPs and tissue inhibitors of MMP (TIMPs) in C. pneumoniae-infected SMC using reverse transcription-polymerase chain reaction analysis. Chlamydial infection of SMC up-regulated the mRNA levels of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) but did not affect the expression of MMP-2 and -9 (gelatinases). Additionally, the levels of TIMP-1 and -2 mRNA remained unchanged upon infection. Cells infected with C. pneumoniae secreted increased quantities of MMP-1 and -3 proteins as demonstrated by enzyme-linked immunosorbent assays. The ability of C. pneumoniae to stimulate the production of MMP-1 and -3 by SMC may be important for its pathogenic role in the progression of atherosclerotic disease.
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PMID:Increased production of matrix metalloproteinases 1 and 3 by smooth muscle cells upon infection with Chlamydia pneumoniae. 1312 50

Chlamydia pneumoniae infection has been linked to atherosclerosis, but a possible relationship with venous thromboembolism (VTE) had not been sought. We determined circulating anti-C. pneumoniae antibody levels in patients with VTE. Fifty-four percent of the cases and 15.9% of the controls had specific IgG titers of at least 256 (p<0.0001). The crude odds ratio for VTE was 6.2 (95% CI, 3.8-10.1), and rose to 7.7 (4.5-13.2) after excluding subjects carrying the factor V Arg 506 Gln or factor II G 20210 A mutations. Other studies did not confirm such an association or found a lower odds ratio. This association remains to be confirmed in other case-control or prospective studies.
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PMID:Infection and venous thrombosis. 1367 72

Chlamydia pneumoniae infection has been linked with atherosclerosis. However, the mechanism responsible for the atherogenic effects of C pneumoniae remains unclear. Heat shock proteins (HSPs) have been found in atherosclerotic lesions. HSPs of HSP70 and HSP90 families are involved in the regulation of cell cycle progression and cell proliferation. We assessed the hypothesis that HSP60 is induced in vascular cells infected with C pneumoniae and stimulates cell proliferation. Rabbit vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were infected with C pneumoniae. Western blot analysis demonstrated the induction of endogenous HSP60 expression in C pneumoniae-infected VSMCs. C pneumoniae infection significantly increased the number of VSMCs, and the mitogenic effect correlated with the expression level of endogenous HSP60. In contrast to VSMCs, C pneumoniae infection had no effect on the expression level of HSP60 and did not stimulate cell proliferation in HUVECs. Exogenous addition of recombinant chlamydial HSP60 had no mitogenic effect on VSMCs and HUVECs. However, overexpression of HSP60 within VSMCs by infection with adenovirus encoding human HSP60 resulted in a significant increase in cell numbers compared with uninfected VSMCs. These results suggest that overexpression of endogenous HSP60 may be a central intracellular event responsible for the mitogenic effects induced by C pneumoniae infection. In addition to C pneumoniae, other infectious agents and atherogenic risk factors may also stimulate VSMC proliferation and contribute to the lesion formation through the induction of HSP60.
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PMID:Chlamydia pneumoniae stimulates proliferation of vascular smooth muscle cells through induction of endogenous heat shock protein 60. 1450 Mar 33

Chlamydia pneumoniae infection is associated with atherosclerosis and may be an emerging risk factor in coronary artery disease. C. pneumoniae can infect, multiply within and modulate the function of all atheroma cell types. Specific chlamydial virulence determinants have been identified that permit interaction with host cells and dysregulate cell function. In particular, chlamydial heat shock protein 60 and lipopolysaccharide may modulate cell function to dysregulate lipid metabolism, induce inflammatory cytokine cascades and trigger production of cross-reactive antibodies that initiate and promote atherogenesis. This paper reviews chlamydial heat shock protein 60 and lipopolysaccharide as potential virulence determinants in atherogenesis.
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PMID:Chlamydial heat shock protein 60 and lipopolysaccharide: potential virulence determinants in atherogenesis. 1456 Nov 89

Though Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis, its role in early atherogenesis has not been well elucidated. To clarify whether C. pneumoniae infection was related to early atherogenesis, we evaluated the association between serological detection of C. pneumoniae antibodies and aortic stiffness in 102 healthy young male volunteers (mean age 27.1+/-0.4 years). Serum C. pneumoniae IgA and IgG antibodies were measured by the enzyme-linked immunosorbent assay (ELISA). Aortic stiffness was estimated using the brachial-ankle pulse wave velocity (PWV). No significant differences were observed between IgA seropositive and seronegative groups with regard to conventional cardiovascular risk factors. However, the mean PWV value was significantly higher in the IgA seropositive group than the seronegative group. Analyses of subgroups according to C-reactive protein (CRP) level showed that those subjects with IgA seropositivity and a high CRP level (>0.17 mg/l) had the highest PWV values. Multivariate logistic regression analysis revealed that a combination of C. pneumoniae IgA seropositivity and a high CRP level was an independent predictor of high values of PWV. These results suggest that C. pneumoniae infection might contribute to early atherogenesis, which might be associated with chronic inflammation.
Atherosclerosis 2003 Nov
PMID:Influence of Chlamydia pneumoniae infection on aortic stiffness in healthy young men. 1464 13

Although the metabolic syndrome together with insulin resistance and their consequences are probably basic factors in pathogenesis of atherosclerosis, inflammatory and infectious aspects of this process are unquestionable only in some of the patients. Endothelial dysfunction was identified both in the experiment and in patients after herpes virus simplex 1 infection, cytomegaloviral infection, Chlamydia pneumoniae infection, or Helicobacter pylori infection. However, it is not clear whether it is always caused by direct specific activity of a given pathogen or whether it is a result of inflammatory cytokines activity, heat shock protein activity, or CRP activity. In recent years secondary antibiotic prevention in patients after myocardial infarction has been discussed. Lower mortality rate from acute myocardial infarction and cerebral vascular accidents were found in several observations of patients vaccinated against influenza. In patients with non-stable angina pectoris we have found significantly more frequent occurrence of IgG antibodies against Chlamydia pneumoniae. This occurrence was more frequent in diabetics compared to non-diabetics. Endothelia exposed to cyto-megaloviral infection exprimed adhesive molecules on their surfaces. After an increase of the concentration of glucose in medium to 11.0 mmol/l and 16.5 mmol/l the expression of adhesive molecules after cyto-megaloviral infection increased. Relationship of infection, inflammation, and atherosclerosis has been a subject of intensive investigation in recent years. Discussion of possible consequences of these findings, especially from viewpoint of atherosclerosis prevention and its organ complications, is of the same intensity. Hypothesis about participation of infection and inflammation in pathogenesis of atherosclerosis seems to be very attractive. In spite of the fact that findings supporting this hypothesis cumulate final conclusion can't be made yet.
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PMID:[Infectious and inflammatory factors in the etiology and pathogenesis of atherosclerosis]. 1504 Jan 64


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