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)

Antibodies to Helicobacter pylori, Chlamydia spp. and Mycobacterium bovis were determined in patients with coronary heart disease, H. pylori-related dyspepsia, and tuberculosis, and healthy controls. Enzyme-linked immunosorbent assay was conducted with a glycine extract and CagA protein of H. pylori, chlamydial lipopolysaccharide and mycobacterial heat shock protein Hsp65. The prevalence of anti-glycine extract IgG in coronary heart disease patients was higher than in the tuberculosis group and controls, and the same as in dyspeptic patients. Anti-chlamydial IgG were more prevalent in the coronary heart disease group than in healthy subjects. There was no difference in the prevalence of anti-CagA IgG in the coronary heart disease group and controls or anti-Hsp65 IgG in the patients with coronary heart disease, dyspepsia, tuberculosis, and controls. Anti-glycine extract IgA (like anti-glycine extract IgG) were more prevalent in the coronary heart disease group than in the healthy group. The highest anti-glycine extract IgG/IgA and anti-chlamydial IgG titers were more frequent in coronary heart disease patients as compared with controls. Infections with H. pylori and Chlamydia spp. and enhanced production of antibodies to these pathogens may predispose to human atherosclerosis.
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PMID:A link between Helicobacter pylori and/or Chlamydia spp. infections and atherosclerosis. 1273 90

Thrombin contributes to hemostasis by activating platelets, the formation of fibrin, and contraction of the injured vessel. These effects are mediated through the proteolytic activity of thrombin. We hypothesized that thrombin may have a role in vasospasm after arterial injury and examined the physiologic and cellular signaling events of thrombin in intact vascular smooth muscles. Thrombin stimulation of strips of bovine carotid artery smooth muscle led to contractions which relaxed with the addition of the nitric oxide donor, sodium nitroprusside. However, washout of the thrombin and SNP resulted in the re-generation of force. This was not observed with other agonists such as endothelin, thromboxane analogues, or serotonin. Using two-dimensional immunoblotting we demonstrate that thrombin stimulation leads to increases in the tyrosine phosphorylation of 4 proteins, three different isoforms of P44 mitogen activated protein kinase (MAPK) and one isoform of P38 stress activated protein kinase (SAPK). Activation of P38 SAPK leads to activation of MAPKAP kinase-2 and a major substrate protein of MAPKAP kinase-2 is the small heat shock protein, HSP27. HSP27 has been implicated in mediating smooth muscle contraction. These data suggest that in the setting of arterial injury, thrombin-induced contraction may supercede over short acting vasorelaxants such as NO resulting in vasospasm. In addition to stress, physiologic substances such as thrombin, activate SAPKs leading to increases in the phosphorylation of HSP27. Thus, thrombin may play a central role in hemostasis after vascular injury and in the pathologic responses to plaque rupture and thrombosis in atherosclerosis.
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PMID:Thrombin contraction of vascular smooth muscle: implications for vasospasm. 1277 50

Chlamydia pneumoniae (C. p.) is very frequently cited as an important factor of the origin of atherosclerosis. To confirm the diagnostic value of the serological examination the following reactions have been used: microimmunofluorescence reaction (MIF) for estimating of antibodies against major outer membrane proteins C. p. (anti-MOMP) and ELISA for detecting antibodies against the lipopolysacharides of C. p. (anti-LPS), both in IgA and IgG immunoglobulin classes of the serum. The ELISA for the detection of the IgG antibodies against chlamydial heat shock protein (cHSP60) has been used. The sera of 155 patients suffering from acute myocardial infarction (AMI) and 69 patients with unstable angina pectoris (UAP) have been examined. The heart disease has been confirmed by anamnesis, electrocardiography and coronarography. As a control group the sera from 112 persons without sings of a heart disease were examined. The antibodies against the cHSP60 have been determined only in the sera 69 patients with UAP and 49 control sera. Statistically higher occurrence of the antibodies anti-MOMP C. p. in the IgA class sera of patients suffering from UAP has been noted compared with those found in the sera of the control group (chi 2 = 18.56; p < 0.01). In the globulin IgG class of the both groups no difference has been found. The anti-LPS C. p. antibodies in the IgA as well in IgG anti-LPS classes of the patients sera with UAP were present significantly more frequently than in the control group (chi 2 = 11.49; p < 0.01, chi 2 = 4.16; p < 0.05). Similarly the incidence of the anti-LPS C. p. antibodies in the IgA class sera of 155 patients suffering from AMI was significantly higher than in the control group (chi 2 = 8.55; p < 0.01). The anti-cHSP60 antibodies have been found in 41 out of 69 patients suffering from UAP (59.4%) and in 21 of 49 control individuals (42.9%). The results seem to confirm an important role of C. p. in atherogenesis. The monitoring of the antibodies against the C. p. may supplement the diagnostics in patients suffering from UAP and AMI and the efficacy of its therapy and prevention as well.
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PMID:[Serologic study of atherosclerosis and its vascular complications]. 1466 61

Excessive proliferation of vascular smooth muscle cells (VSMCs) is a critical element in the development of several vascular pathologies, particularly in atherosclerosis and in restenosis due to angioplasty. We have shown that butyrate, a powerful antiproliferative agent, a strong promoter of cell differentiation and an inducer of apoptosis inhibits VSMC proliferation at physiological concentrations with no cytotoxicity. In the present study, we have used cDNA array technology to unravel the molecular basis of the antiproliferative effect of butyrate on VSMCs. To assess the involvement of gene expression in butyrate-inhibited VSMC proliferation, proliferating VSMCs were exposed to 5 mmol/l butyrate 1 through 5 days after plating. Expression profiles of 1.176 genes representing different functional classes in untreated control and butyrate treated VSMCs were compared. A total of 111 genes exhibiting moderate (2.0-5.0 fold) to strong (> 5.0 fold) differential expression were identified. Analysis of these genes indicates that butyrate treatment mainly alters the expression of four different functional classes of genes, which include: 43 genes implicated in cell growth and differentiation, 13 genes related to stress response, 11 genes associated with vascular function and 8 genes normally present in neuronal cells. Examination of differentially expressed cell growth and differentiation related genes indicate that butyrate-inhibited VSMC proliferation appears to involve down-regulation of genes that encode several positive regulators of cell growth and up-regulation of some negative regulators of growth or differentiation inducers. Some of the down-regulated genes include proliferating cell nuclear antigen (PCNA), retinoblastoma susceptibility related protein p130 (pRb), cell division control protein 2 homolog (cdc2), cyclin B1, cell division control protein 20 homolog (p55cdc), high mobility group (HMG) 1 and 2 and several others. Whereas the up-regulated genes include cyclin D1, p21WAF1, p141NK4B/p15INK5B, Clusterin, inhibitor of DNA binding 1 (ID1) and others. On the other hand, butyrate-responsive stress-related genes include some of the members of heat shock protein (HSP), glutathione-s-transferase (GST), glutathione peroxidase (GSH-PXs) and cytochrome P450 (CYP) families. Additionally, several genes related to vascular and neuronal function are also responsive to butyrate treatment. Although involvement of genes that encode stress response, vascular and neuronal functional proteins in cell proliferation is not clear, cDNA expression array data appear to suggest that they may play a role in the regulation of cell proliferation. However, cDNA expression profiles indicate that butyrate-inhibited VSMC proliferation involves combined action of a proportionally large number of both positive and negative regulators of growth, which ultimately causes growth arrest of VSMCs. Furthermore, these butyrate-induced differential gene expression changes are not only consistent with the antiproliferative effect of butyrate but are also in agreement with the roles that these gene products play in cell proliferation.
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PMID:Gene expression profile of butyrate-inhibited vascular smooth muscle cell proliferation. 1467 79

An immune response to heat shock protein (HSP)-60/65 has recently been implicated in atherogenesis. The aim of this study was to determine whether this effect may be mediated by impairment of endothelial function. Rabbits were injected with bacillus Calmette-Guerin (BCG) vaccine (n=12) or saline (n=12). A further injection of BCG or saline was administered after 2 weeks. After a further 2 weeks, animals were fed either a 0.25-1% cholesterol diet or a chow diet for 16 weeks. Blood cholesterol levels were maintained at 10-12mmol/l by altering the dietary cholesterol content. Plasma levels of anti-mycobacterial antibodies rose following BCG immunisation, but anti-HSP antibodies developed only in the BCG-immunised, cholesterol-fed rabbits. Aortic endothelium from cholesterol-fed, but not chow-fed, rabbits stained positively for HSP-60, independently of the immunisation protocol. Endothelial function was impaired in the BCG immunised, cholesterol-fed rabbits as measured by acetylcholine-mediated relaxation of isolated non-atherosclerotic carotid artery rings (P<0.05). This impairment was positively associated with the level of plasma anti-HSP-60 antibodies (P<0.01). These results suggest that BCG immunisation impairs endothelial responses, at least in part, by immune responses against mycobacterial and vascular HSP.
Atherosclerosis 2004 Jan
PMID:Impairment of vascular function following BCG immunisation is associated with immune responses to HSP-60 in the cholesterol-fed rabbit. 1470 52

Current evidence lends increasing support to immunoinflammatory mechanisms as one of the prime pathogenic processes involved in the development and progression of atherosclerosis. It has been observed that most human beings have cellular and humoral reactions against microbial heat shock protein (HSP). Autoantibody levels against HSPs are significantly increased in patients with atherosclerosis and T lymphocytes specifically responding to HSPs have been demonstrated within atherosclerotic plaques. Most of the known risk factors for atherosclerosis, viz. oxidized low-density lipoprotein, hypertension, infections and oxidative stress, evoke increased expression of HSPs in endothelial cells, smooth muscle cells and macrophages, the main cellular constituents of atherosclerotic plaques. Evolutionary conservation has resulted in a high degree of sequence homology between microbial and human HSPs and hence the immune reactions against microbial HSPs carry a risk of being misdirected towards human HSPs expressed in the stressed cells of the blood vessels. HSPs and anti-HSP antibodies have been shown to elicit production of pro-inflammatory cytokines by macrophages and adhesion molecules by endothelial cells in various in vitro and animal model studies. These autoimmune reactions to HSPs expressed in the vascular tissue can contribute to both initiation and perpetuation of atherosclerosis.
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PMID:Autoimmunity to heat shock proteins in atherosclerosis. 1500 85

Atherosclerosis is an inflammatory disease. Both innate and adaptive immunity are involved in lesion formation and development. A number of antigen candidates, such as oxidized low-density lipoprotein and heat shock protein, have been associated with the inflammation and immune reaction that is part of the atherosclerotic process. Because experimental models of some other inflammatory/autoimmune diseases can be improved by vaccination, it is of interest to investigate if vaccination can also be applied to prevent or retard atherosclerosis. Indeed, the modification of immune responses in animal models can greatly affect the development and progression of atherosclerosis. This review provides an overview of our current understanding of effects and proposed mechanisms of immunization on preventing atherosclerosis.
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PMID:Vaccination and atherosclerosis. 1502 1

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

Retrospective and cross-sectional studies have suggested that both bacterial and viral infections may be risk factors for atherosclerosis, ischemic stroke and acute coronary events. The correlation between Chlamydia pneumoniae and atherosclerosis remains a source of controversy. Our case-control study is aimed at evaluating the frequency of C. pneumoniae infection in a cohort of young adults with recent cerebrovascular disease and in particular etiologic stroke subtypes. Chlamydia pneumoniae IgG, IgM and IgA antibodies were evaluated by microimmunofluorescence method and antibody titers to both recombinant antigens chlamydial outer protein 2 and 60-kDa chlamydial heat shock protein (HSP60) by ELISA. The two groups differed with regard to the prevalence of C. pneumoniae IgA (P < 0.001) and IgG (P < 0.0001), as well as the titer of anti-R-HSP60 IgG (P < 0.001). We found an increase in IgA titers, suggestive of persistent, chronic active infection, in 16 patients in whom the etiology of the cerebral ischemic event was large-vessel atherothrombosis. Persistent, active C. pneumoniae infection may be an additional risk factor for ischemic stroke mainly of atherotrombotic origin in young subjects. However, a large-scale prospective confirmation of our findings is required.
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PMID:Chlamydia pneumoniae infection in young stroke patients: a case--control study. 1514 25

Atherosclerosis is a chronic disease that causes various cardiovascular complications. Although the initiation and progression of atherosclerosis largely depend on genetic factors and life styles, the cellular and molecular mechanisms are still not clear. Recent studies have revealed that cellular and humoral immunity plays crucial roles in atherogenic lesion formation, including macrophages, CD4+ and CD8+ T cells and dendritic cells as well as autoantigens such as heat shock protein (HSP 60/65) and oxidized LDL. Furthermore, atherosclerosis is associated with microbial or viral infection. Given these recent advances, various modifications of the immune system in mouse models have been performed to determine the underlying mechanisms of atherogenesis and new therapeutic strategies. Blocking of macrophage inducing factors or disruption of scavenger receptors on macrophages such as SR-A and CD36 can inhibit atherosclerosis progression. Switching the immune system of CD4+ T cells from Th1 to Th2 can induce secretion of anti-inflammatory cytokine IL-10, leading to decreased atherosclerotic lesions. Eradication of microbes and viruses can also reduce atherosclerosis. These investigations strongly support that immune responses are important mechanisms of atherogenesis, and immunomodulation can be a new strategy to treat atherosclerosis.
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PMID:Atherosclerosis: immunopathogenesis and immunotherapy. 1550 66


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