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)

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

To identify T- and/or cross-reactive B-cell epitopes of P. gingivalis and human heat-shock protein (HSP)60 in atherosclerosis patients, we synthesized 104 overlapping synthetic peptides spanning whole molecules of P. gingivalis HSP60 and human HSP60, respectively. T-cell epitopes of P. gingivalis HSP were identified with the use of previously established P. gingivalis HSP-reactive T-cell lines. B-cell epitopes of P. gingivalis HSP60 and human HSP60 were identified by the use of patients' sera. Anti-P. gingivalis, anti-P. gingivalis HSP60, or anti-human HSP60 IgG antibody titers were higher in the atherosclerosis patients compared with the healthy subjects. Five immunodominant peptides of P. gingivalis HSP60, identified as T-cell epitopes, were also found to be B-cell epitopes. Moreover, 6 cross-reactive B-cell epitopes of human HSP60 were identified. It was concluded that P. gingivalis HSP60 might be involved in the immunoregulatory process of atherosclerosis, with common T- and/or B-cell epitope specificities and with cross-reactivity with human HSP60.
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PMID:Epitope mapping of Porphyromonas gingivalis heat-shock protein and human heat-shock protein in human atherosclerosis. 1555 1

Chlamydia pneumoniae uses blood monocytes (PBMC) for systemic dissemination, persists in atherosclerotic lesions, and has been implicated in the pathogenesis of atherosclerosis. During transmigration in a newly developed transendothelial migration model (TEM) C. pneumoniae-infected PBMC spread their infection to endothelial cells. Transmigrated PBMC retained their infectivity and transmitted the pathogen to smooth muscle cells in the lower chamber of the TEM. Detection of chlamydial HSP60 mRNA proved pathogen viability and virulence. We conclude that PBMC can spread chlamydial infection to vascular wall cells and we suggest the TEM as a novel tool to analyze host-pathogen interactions in vascular chlamydial infections.
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PMID:Transmission of Chlamydia pneumoniae infection from blood monocytes to vascular cells in a novel transendothelial migration model. 1562 38

The highly conserved and ubiquitous heat shock proteins (HSP) are essential for the cellular homeostasis and efficiently trigger cellular responses to stress conditions. Both microbial and human HSP act as dominant antigens in numerous infectious and autoimmune diseases such as atherosclerosis, inducing a strong immune-inflammatory response. In the present study, the surface localization of HSP60 on stressed and unstressed human umbilical venous endothelial cells (HUVECs) was investigated using sensitive high resolution microscopy methods and flow cytometry. Confocal laser scanning microscopy (CLSM) revealed an increase of HSP60 in the mitochondria and on the surface of heat-stressed living and fixed HUVECs compared to unstressed cells. Atomic force microscopy (AFM), which has developed as sensitive surface-probe technique in biology, confirmed the presence of HSP60 on the membrane of stressed cells at an even higher lateral resolution by detecting specific single molecule binding events between the monoclonal antibody AbII-13 tethered to AFM tips and HSP60 molecules on cells. The interaction force (force required to break a single AbII-13/HSP60 bond) was 59+/-2 pN, which correlated nicely to the 51+/-1 pN measured with isolated HSP60 attached to mica surfaces. Overall, we found clear evidence for the occurrence of HSP60 on the surface of stressed HUVECs in a very similar patchy distribution pattern in living and fixed cells. The relevance of our findings with respect to the role of HSP60 in atherogenesis is discussed.
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PMID:Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy. 1578 82

Over the past number of years numerous data have been published regarding increased atherosclerosis in patients with systemic lupus erythematosus (SLE), and it has been shown that premature or accelerated atherosclerosis is an important cause of morbidity and mortality in these patients. Besides the traditional risk factors for cardiovascular disease, the association between SLE and atherosclerosis can be attributed to additional risk factors closely related to inflammation and autoimmunity. In particular, several autoantibodies and their respective autoantigens have been identified as possible factors in the development and progression of the atherosclerotic process in SLE. The understanding of SLE-related risk factors for enhanced atherosclerosis could shed more light on disease mechanisms, leading to new therapeutic strategies for the treatment of cardiovascular diseases in SLE patients. In the present paper, the biological characteristics and possible pathogenetic role of the oxidized low-density lipoprotein (oxLDL) and anti-oxLDL, beta(2)-glycoprotein I (beta(2)GPI) and anti-beta(2)GPI, and heat-shock protein 60/65 (HSP60/65) and anti-HSP60/65 autoantibody systems are summarized.
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PMID:Systemic lupus erythematosus, atherosclerosis, and autoantibodies. 1612 77

Recent evidence has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis. A significant association has also been detected between heat shock protein (HSP) 60 antibody and the severity of coronary atherosclerosis. The aim of this study was to define the relationship between instability of ischemic heart disease (IHD) and serum levels of HSP60 and C. pneumoniae antibodies. Blood samples for the measurement of serum antibody titers were obtained from 1131 patients with ischemic heart disease (65+/-9 years; male/female, 828/303) and 127 non-IHD controls with normal coronary arteries (64+/-9 years; male/female, 60/67) on the day of cardiac catheterization. The serum levels of anti-human HSP60 IgG antibody and anti-chlamydial IgM, but not IgG or IgA, antibody were significantly higher in ACS patients than in stable IHD patients or controls. These results suggest that acute C. pneumoniae infection with HSP60-related immunological responses may contribute to the pathophysiology of acute coronary syndromes.
Atherosclerosis 2005 Nov
PMID:Acute Chlamydia pneumoniae infection with heat-shock-protein-60-related response in patients with acute coronary syndrome. 1621 93

Infection, in particular by Chlamydia pneumoniae (Cp), has been associated with atherosclerosis and coronary heart disease. Immune reactions to heat shock proteins (HSPs) have been advocated to link infection to atherosclerosis and its acute sequelae based on molecular mimicry with host HSPs. We have here evaluated the role played by recombinant Cp-HSP60 and Cp-HSP10 for their ability to induce maturation of human monocyte-derived dendritic cells (MDDC) and T cell polarization. Cp-HSP60, but not Cp-HSP10, induced a strong MDCC maturation, as assessed by the expression of co-stimulatory molecules and other markers. Secretion of regulatory cytokines and enhancement of antigen presenting ability of mature (m)MDDC toward a clear T helper (Th) 1 pattern were also induced by Cp-HSP60. An analysis of the IL-12 cytokine family demonstrated that Cp-HSP60-matured MDDC were able to express p35 and p40 mRNA subunits to form IL-12, and p19 and p40 subunits to form IL-23. Thus, preferential Th1 polarization of immune response induced by Cp-HSP60-matured MDDC appears to be due to the concomitant expression of IL-12 and IL-23. Our data suggest that Cp-HSP60-matured DC may contribute to T-cell mediated immunopathology of atherosclerosis via a chronic stimulation of Th1 immune responses.
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PMID:60-kDa heat shock protein of Chlamydia pneumoniae promotes a T helper type 1 immune response through IL-12/IL-23 production in monocyte-derived dendritic cells. 1646 Sep 83

Inflammatory processes contribute to the pathogenesis and complications of atherosclerosis and coronary heart disease (CHD). Several findings indicate that chlamydial heat shock proteins (HSP) may represent a particularly strong antigenic stimulus, able to induce specific humoral (Ab) and T-cell-mediated immune responses (CMI) linking infection by Chlamydia pneumoniae (CP) to immuno-pathological sequelae such as atherosclerosis and CHD. We have here evaluated the ability of chlamydial recombinant (r) HSP60 and rHSP10 to induce specific immune responses in human peripheral blood lymphocytes and in murine models. rHSP60, but not rHSP10, was shown to induce proliferation and Interferon-gamma secretion in lymphocytes of randomly selected blood donors, as well as to generate and detect delayed-type hypersensitivity response in HSP60-vaccinated mice. Overall, the present study provides new hints to evaluate a previous exposition to CP using rHSP60 in humans. Thus the evaluation of specific HSP60 CMI response in healthy subject could be useful to monitor the reactivity to Chlamydia pneumoniae possibly providing a link to CHD pathologies.
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PMID:60-kDa heat shock protein of Chlamydia pneumoniae is a target of T-cell immune response. 1660 28

Heat shock proteins (HSPs) of endogenous and exogenous origin are suspected contributors to the initiation and aggravation of vascular pathologies like atherosclerosis and restenosis. Toll-like receptors (TLRs) 2 and 4 are well-known receptors for exogenous pathogen-associated molecular patterns and have recently been thought to play a role in HSP60-induced cellular activation. We hypothesized that human HSP60 directly stimulates venous smooth muscle cell (VSMC) proliferation through a TLR-dependent mechanism. Localization of HSP60, TLR2 and TLR4 was studied in failed venous grafts and normal venous tissue by double immunostaining. In vitro VSMCs were incubated for 48 h with recombinant human HSP60. In other experiments, VSMCs were pre-incubated for 30 min with specific anti-TLR2 and anti-TLR4 antibodies. VSMC proliferation was determined by Ki67 immunoreactivity, and mean values were compared between experimental and control groups. In addition, human embryonic kidney (HEK) cells transfected with human TLR2 or TLR4/MD-2 were exposed to HSP60 for 48 h, and proliferation was determined by using a hemocytometer. Co-localization of HSP60 and TLRs was detected in all neointimal lesions but was virtually absent in normal veins. Human HSP60 stimulated VSMC proliferation in a concentration-dependent fashion. In addition, TLR2 and TLR4 antibodies attenuated VSMC proliferation. The role of TLR-mediated stimulation of cell proliferation by HSP60 was supported by the significant increase in proliferation of transfected HEK cells. These findings provide supporting evidence for the role of HSP60 and TLR2 and TLR4 in vascular disease. Moreover, our data surpass the infection- and autoimmunity-based hypotheses of cardiovascular disease and suggest an additional HSP60-related autocrine process.
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PMID:Human heat shock protein 60 stimulates vascular smooth muscle cell proliferation through Toll-like receptors 2 and 4. 1684 93

Autoimmune reactions to HSP60 are believed to play a key role during development of early atherosclerosis. Due to the high degree of phylogenetic conservation between microbial and human HSP60, bacterial infections might be responsible for inducing cross-reactivity to self HSP60, which is expressed on the surface of arterial endothelial cells stressed by classical atherosclerosis risk factors. Conformational epitopes recognized by polyclonal anti-mycobacterial HSP60 antibodies from subjects with atherosclerosis were identified using a phage displayed random library of cyclic constrained 7mer peptides. After five rounds of selection, DNA sequencing of strongly binding clones revealed that one peptide motif (CIGSPSTNC) was present in 64% of all clones, and a second motif (CSFHYQNRC) in 14%. Using a newly developed method for structural alignment of small constrained peptides onto a protein surface, we located the motif present in 14% of all clones on the surface of mycobacterial HSP60. The motif present in 64% of all clones was found on the surface of mycobacterial HSP60 as well as in the homologous region of human HSP60, which makes this epitope a promising candidate for further investigations on cross-reactive epitopes involved in early atherogenesis.
Atherosclerosis 2007 Sep
PMID:Identification of atherosclerosis-associated conformational heat shock protein 60 epitopes by phage display and structural alignment. 1709 62


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