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)

Alterations in the level and distribution of arterial heat shock proteins (HSPs) have been demonstrated during atherogenesis. The significance of these changes within the developing and dying plaque, however, is not understood. To examine a potential protective effect of HSPs on arterial cells, enzymatically isolated cells from normal and diet-induced atherosclerotic aortas of cynomolgus macaques were stressed for 20 h with and without added 72/73 kDa heat shock proteins (HSP-72/73), over a range of temperatures and dosages. Cells were analyzed for changes in viability and lysosomal membrane integrity. The responses of cells from normal and diseased aortas for all test regimens were similar. Viability and lysosomal membrane integrity of untreated cells were correlated (r = 0.85), and both factors declined with increasing thermal stress (P less than 0.0005 and P less than 0.004, respectively). Exogenous HSP-72/73 increased cell viability after stress at a minimum concentration of 10 micrograms/ml (P less than 0.05) but was not concentration dependent. Response to different temperatures showed exogenous HSP-72/73 increased cell survival at all temperatures, with the greatest effect at 37 degrees C (P less than 0.01). In contrast, HSP-72/73 did not have an effect on lysosomal membrane integrity for the test period studied. The results demonstrate exogenous HSP-72/73 increases arterial cell survival, suggesting these proteins are associated with a protective mechanism in normal and diseased arteries.
Atherosclerosis 1990 Oct
PMID:Effect of heat shock proteins on survival of isolated aortic cells from normal and atherosclerotic cynomolgus macaques. 228 91

Investigations in rabbits and humans have provided experimental evidence that autoimmune reactions play a major role in the initial stages of the development of atherosclerosis. These involve the infiltration of the arterial intima with T cells reacting with heat shock protein (hsp) 65/60 and the occurrence of anti-hsp 65/60 antibodies. This early immunologically mediated stage of atherosclerosis is still reversible but if additional risk factors, such as high cholesterol levels, come into effect, severe mostly irreversible lesions develop.
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PMID:Role of heat shock protein 65/60 in the pathogenesis of atherosclerosis. 754 57

Atherosclerosis is a multifactorial vascular disorder responsible for the highest rate of mortality in the western world. During the last decades, research on this disease has primarily focused on the role of lipids, which are essential to the formation of lesions in the vascular intima that ultimately leads to clinically apparent atherosclerotic plaques. More recently, several anecdotal findings have indicated the possible involvement of the immune system in the process of atherogenesis. In particular, the appearance of immunocompetent cells as well as humoral antibodies in the intima in the early stages of disease development supports the view of an inflammatory component in this disorder. In addition to the search for lipid-associated antigens that might entail full-blown atherosclerosis, other candidate antigens capable of inducing an immune response in the vascular wall have also been explored. Within the probable group of antigens for immune responsiveness, heat shock protein (hsp) 60/65 became a serious candidate, upon observation that immunization of rabbits with this protein led to arteriosclerotic changes of the aortic intima. In the last few years we have established this rabbit model for immunologic investigations of atherosclerosis and, in parallel, examined the pathogenesis of human atherosclerosis with regard to hsp 60/65 immune reactivity. Currently available data point to an autoimmune induction of early inflammatory arteriosclerotic changes triggered by a cellular and humoral immune reaction to stress-induced hsp 60-expressing areas of the endothelial cells.
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PMID:Atherosclerosis as an autoimmune condition. 759 81

Atherosclerotic plaques harbour 3 main cell types: arterial smooth muscle cells, monocyte-macrophages and T-lymphocytes. Together with other morphological characteristics, this feature concurs to the view that plaques are foci of chronic inflammation. The presence of T-cells suggests that immune mechanisms are involved in the development of atherosclerosis. Clinical studies have found correlations between the presence or progression of carotid plaques and the serum concentration of antibodies against oxidized low-density lipoproteins and against heat shock protein HSP-65. Along with other observations, these correlations, if confirmed and extended, may open new avenues to understand the triggering mechanisms of atherosclerosis. However, the available evidence is still insufficient to establish that an autoimmune involvement is a cause rather than a consequence of atherosclerosis.
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PMID:[Immunity, inflammation and atherosclerosis]. 799 33

The purpose of this study was to establish the estrogen receptor (ER) expression and content in human aorta fragments removed at the time of by-pass surgery. To this end, we adopted a radioligand binding assay to evaluate either soluble (S) or nuclear (N) ER using dextran-coated charcoal (DCC) and filtration methods, respectively. To better define the intratissular distribution and content of ER, we also measured the presence of a 27 kDa heat shock protein (HSP27), a well established ER-associated protein, using D5 monoclonal antibody. Finally, we analysed the different molecular isoforms of both S and N ER using size exclusion-high performance liquid chromatography (SE-HPLC). High affinity (type I) sites of estrogen binding were detected in 17 out of 19 samples in either S or N fraction, although only 9 out of 19 cases displayed site 1 ER in both cell compartments. ER levels in aortic tissues, detected by radioligand method, compare well with those we have found in other hormone-sensitive human cancer tissues and cells. SE-HPLC analysis revealed two main receptor isoforms in the soluble fraction, having 65 kDa and 18 kDa molecular mass, while a minor component of 29 kDa was also found; the nuclear fraction displayed again two major components of 38 and 23 kDa. Using the HSP27 immunohistochemistry we observed a major staining occurring in smooth muscle cells (SMC), with an increasing intensity towards the lumen. All samples, including the ER negative ones, exhibited some degree of histochemical staining. Using an arbitrary cut-off value, 7 out of 12 samples displayed a highly positive staining, 6 of which showed nuclear ER. Furthermore, SE-HPLC separation indicated the presence of a 64.9 kDa component in the soluble fraction, according to the well known relative molecular mass of ER. Following HSP27 immunohistochemistry, the overall staining intensity in aortic SMC approaches that seen in endometrial and breast epithelia, whilst the muscle ER content is generally lower. Although our data are compatible with a direct role of estrogens in arterial function, the extent of the link with arterial disease remains to be established.
Atherosclerosis 1993 Nov
PMID:Evidence for soluble and nuclear site I binding of estrogens in human aorta. 829 1

Evidence suggests an important role for heat shock proteins (HSPs) in the evolution of atherosclerotic necrotic cores. The present study compared normal-appearing and atherosclerotic aortas obtained from control and diet-induced atherosclerotic cynomolgus macaques and from human autopsies, with respect to the localization and content of 70-kDa HSPs (HSP70). The distribution pattern of HSP70 was determined by immunostaining tissue sections with anti-HSP70 monoclonal antibody against both constitutive and inducible isoforms. Changes in HSP70 staining with developing atherosclerosis were quantitated using video morphometry. Total aortic HSP70 content was evaluated by Western blotting tissue homogenates. In both macaque and human aortas, HSP70 staining was homogeneous in normal-appearing regions, but developed a heterogeneous pattern in the presence of atherosclerosis. Immunostaining for three other HSPs (90, 65, and 28 kDa) confirmed the change as HSP-specific. Video morphometry indicated a significant positive association between severity of atherosclerosis and altered patterns of HSP70 staining. However, Western blots detected no difference in total HSP70 content of either human or macaque aortas with plaque progression. The data suggest HSP70 localization changes in aortas during atherosclerosis evolution without affecting overall aortic HSP70 content. Such changes in HSP70 localization may reflect differences in the cellular response and resistance to cytotoxic conditions present within the plaque, which could influence the expansion of necrotic cores.
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PMID:Atherosclerosis alters the localization of HSP70 in human and macaque aortas. 851 43

Levels of specific antibodies (Ab) against mycobacterial and human heat shock protein (hsp) 65/60 are increased in the sera of patients with atherosclerotic lesions and have been demonstrated to be capable of mediating endothelial cytotoxicity. To clarify the antigen epitopes recognized by these serum Abs, Ab binding to hsp65 deletion mutants (Dms), as well as to overlapping 15-mer and 8-mer hsp65 peptides, was assessed. Western blotting of hsp65 Dms indicated the presence of at least one epitope between amino acid (aa) residues 171 and 276, recognized by both high-titer sera and affinity-purified anti-hsp65/60 Ab. Fluorescence immunoassays using 53 15-mer peptides and Pin ELISA using 526 7-mer peptides demonstrated three distinct, conserved sequences with high affinity to high-titer sera and purified anti-hsp65/60 Ab. Two N-terminal sequences, aa 97-109 and aa 179-187, and one C-terminal sequence, aa 504-512, were identified. These three epitopes recognized by anti-hsp65/60 Ab may serve as autoantigens in certain circumstances in vivo. This phenomenon could contribute to the initiation of atherosclerosis by an autoimmune reaction.
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PMID:Epitope specificity of anti-heat shock protein 65/60 serum antibodies in atherosclerosis. 910 73

Recent data from different laboratories have provided evidence that the first stages of atherosclerosis are inflammatory in nature. Research in the last decades on this multifactorial disease has primarily focussed on the role of lipids, with only a few anecdotal findings suggesting the involvement of the immune system in atherogenesis. Within the group of antigens that may be responsible for this immunoactivation during atherogenesis, heat shock protein (hsp) 65/60 became a serious candidate based on the fact that immunization] of normocholesterolemic rabbits with hsp65 leads to the development of arteriosclerotic lesions in the aortic intima and these primary inflammatory lesions are aggravated by a cholesterol-rich diet, thus completely resembling human fatty streaks and atherosclerotic plaques. Furthermore, T cells in atherosclerotic lesions of rabbits have been shown to react specially with mycobacterial hsp65, suggesting that cell-mediated immune responses to hsp60 are also involved in the pathogenesis of this disease In a large epidemiological study we demonstrated that serum antibodies to mycobacterial hsp65 were significantly increased in clinically healthy subjects with sonographically demonstrable carotid atherosclerosis. These antibodies crossreact with human hsp60. Thus further elucidation of the role of the role of the immune system in atherogenesis could enhance our understanding of the mechanism of this vascular disorder, and may lead to new therapeutic strategies for atherosclerosis.
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PMID:The role of (auto-) immunity in atherogenesis. 1040 99

Recent data suggest that the immune system is involved in atherogenesis. Thus, interest has been raised as to the possible antigens that could serve as the initiators of the immune reaction. In the current work, we studied the effects of immunization with recombinant heat shock protein-65 (HSP-65) and HSP-65-rich Mycobacterium tuberculosis (MT) on early atherogenesis in C57BL/6J mice fed either a normal chow diet or a high-cholesterol diet (HCD). A rapid, cellular immune response to HSP-65 was evident in mice immunized with HSP-65 or with MT but not in the animals immunized with phosphate-buffered saline (PBS) alone. Early atherosclerosis was significantly enhanced in HCD-fed mice immunized with HSP-65 (n=10; mean aortic lesion size, 45 417+/-9258 microm2) or MT (n=15; 66 350+/-6850 microm2) compared with PBS-injected (n=10; 10 028+/-3599 microm2) or nonimmunized (n=10; 9500+/-2120 microm2) mice. No fatty streak lesions were observed in mice fed a chow diet regardless of the immunization protocol applied. Immunohistochemical analysis of atherosclerotic lesions from the HSP-65- and MT-immunized mice revealed infiltration of CD4 lymphocytes compared with the relatively lymphocyte-poor lesions in the PBS-treated or nonimmunized mice. Direct immunofluorescence analysis of lesions from HSP-65- and MT-immunized mice fed an HCD exhibited extensive deposits of immunoglobulins compared with the fatty streaks in the other study groups, consistent with the larger and more advanced lesions found in the former 2 groups. This model, which supports the involvement of HSP-65 in atherogenesis, furnishes a valuable tool to study the role of the immune system in atherogenesis.
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PMID:Enhanced fatty streak formation in C57BL/6J mice by immunization with heat shock protein-65. 1007 50

The mucosal pathogen Chlamydia trachomatis affects hundreds of millions of people worldwide and is a significant cause of sexually transmitted disease. Although most acute infections can be easily managed, complications often occur that can be especially severe in women. It has been proposed that increased exposure to conserved chlamydial antigens, such as through reinfection or persistent infection, results in chronic inflammation and tissue scarring and contributes to the pathogenesis of endometrial and fallopian tube damage. This immunopathologic damage is believed to be a principal cause of ectopic pregnancy and tubal factor infertility. The chlamydial heat shock protein Hsp60, a homolog of Escherichia coli GroEL, has been identified as one protein capable of eliciting intense mononuclear inflammation. Furthermore, several studies have revealed a correlation between Hsp60 responses and the immunopathologic manifestations of human chlamydial disease. The role of additional antigens in the immunopathologic response to chlamydiae is currently undefined. A prime candidate, however, is the chlamydial GroES homolog Hsp10, which is genetically and physiologically linked to Hsp60. Recent studies provide data to suggest that immune reactivity to Hsp10 is significantly associated with tubal infertility in a chlamydiae-exposed population. Chlamydia pneumoniae is a more recently defined chlamydial species that has been implicated in a variety of ways with chronic disease processes, such as adult onset asthma and atherosclerosis. Evidence indicates that Hsp60 is present in human atheroma and may play a role in lesion development by direct activation of macrophages. Hsp60 causes the elaboration of inflammatory cytokines, the induction of metalloproteinase, and the oxidation of low density lipoprotein. Each of these events is directly associated with the progress of atherosclerosis. Thus, chlamydial heat shock proteins may function in at least two ways to promote chronic disease: first by direct antigenic stimulation and second as signal transducers that result in macrophage activation. These concepts in disease pathology are discussed in the context of chlamydial infections.
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PMID:Chlamydial heat shock proteins and disease pathology: new paradigms for old problems? 1023 Oct 12


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