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)

Although immunocompetent hosts develop protective type 1 helper T cell (Th1) responses in mycobacterial infections, seroepidemiologic studies show that patients with atherosclerosis commonly express high antibody titers against mycobacterial heat shock protein (HSP) 65 and may develop a nonprotective type 2 helper T cell (Th2) response and advanced disease. These studies were undertaken to define mycobacterial dose requirements and kinetics for development of antibodies to HSP65, the Th1 to Th2 shift of immune response, and calcified atherosclerotic lesion development in the apo E-/- mouse. Fourteen-week apo E-/- female mice were treated intraperitoneally (ip) with heat-killed M. bovis Bacillus Calmette-Guerin (BCG), and 14 days later, cross-sections from the ascending aortas were stained for measurement of lesion size and calcium deposition. At 14 days, 0.01-mg BCG induced Th1 responses against HSP65. In contrast, 1-mg BCG induced splenic PGE2-releasing macrophages with a Th1-to-Th2 shift of responses to HSP65, which was PGE2-dependent. Treatment with 1-mg BCG significantly lowered bone density with increases in marrow osteoclastogenesis and development of calcified lesions in the aorta. At 14 days, 0.01-mg BCG induced Th1-dependent HSP65 responses and did not advance atherosclerosis. In contrast, for 1-mg BCG, a PGE2-dependent Th1-to-Th2 shift of responses to HSP65 and evidence of bone resorption are associated with advanced calcified atherosclerotic lesions.
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PMID:Immunologic response enhances atherosclerosis-type 1 helper T cell (Th1)-to-type 2 helper T cell (Th2) shift and calcified atherosclerosis in Bacillus Calmette-Guerin (BCG)-treated apolipoprotein E-knockout (apo E-/-) mice. 1724 Mar 16

This paper reviews the evidence for the interaction of oral disease (more specifically, periodontal infections) with cardiovascular disease. Cardiovascular disease is a major cause of death worldwide, with atherosclerosis as the underlying aetiology in the vast majority of cases. The importance of the role of infection and inflammation in atherosclerosis is now widely accepted, and there has been increasing awareness that immune responses are central to atherogenesis. Chronic inflammatory periodontal diseases are among the most common chronic infections, and a number of studies have shown an association between periodontal disease and an increased risk of stroke and coronary heart disease. Although it is recognised that large-scale intervention studies are required, pathogenic mechanism studies are nevertheless required so as to establish the biological rationale. In this context, a number of hypotheses have been put forward; these include common susceptibility, inflammation via increased circulating cytokines and inflammatory mediators, direct infection of the blood vessels, and the possibility of cross-reactivity or molecular mimicry between bacterial and self-antigens. In this latter hypothesis, the progression of atherosclerosis can be explained in terms of the immune response to bacterial heat shock proteins (HSPs). Because the immune system may not be able to differentiate between self-HSP and bacterial HSP, an immune response generated by the host directed at pathogenic HSP may result in an autoimmune response to similar sequences in the host. Furthermore, endothelial cells express HSPs in atherosclerosis, and cross-reactive T cells exist in the arteries and peripheral blood of patients with atherosclerosis. Each of these hypotheses is reviewed in light of current research. It is concluded that although atherosclerotic cardiovascular disease is almost certainly a multifactorial disease, there is now strong evidence that infection and inflammation are important risk factors. As the oral cavity is one potential source of infection, it is wise to try to ensure that any oral disease is minimised. This may be of significant benefit to cardiovascular health and enables members of the oral health team to contribute to their patients' general health.
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PMID:Cardiovascular and oral disease interactions: what is the evidence? 1746 39

The scavenger receptor-A (SR-A), originally recognized by its ability to internalize modified lipoproteins, has largely been studied in relation to atherosclerosis as well as innate immunity against pathogen infection. SR-A was recently shown to be a receptor on antigen-presenting cell for heat shock protein (HSP) and was implicated in the cross-presentation of HSP-chaperoned antigens. Here, we show that SR-A is not required for antitumor immunity generated by HSP-based (e.g., grp170) vaccine approaches in vivo. The lack of SR-A significantly enhances HSP- or lipopolysaccharide-mediated vaccine activities against poorly immunogenic tumors, indicating that SR-A is able to attenuate immunostimulatory effects of adjuvants or "danger" molecules. The improved antitumor response in SR-A knockout mice is correlated with an increased antigen-specific T-cell response. Moreover, SR-A-deficient dendritic cells are more responsive to inflammatory stimuli and display a more effective antigen-presenting capability compared with wild-type cells. This is the first report illustrating that SR-A negatively regulates antigen-specific antitumor immunity, which has important clinical implications in vaccine design for cancer immunotherapy.
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PMID:Scavenger receptor-A negatively regulates antitumor immunity. 1751 Apr 31

Immunoinflammatory processes due to chronic infection are thought to be one of the definitive atherogenetic processes. Especially, anti-heat shock protein antibodies have been related to the prevalence of disease such as coronary artery disease or cerebral infarction, etc., resulted from atherosclerosis. Furthermore, the presence of HSP60-specific T lymphocytes in circulation may increase the risk of atherosclerosis. We have recently demonstrated the evidences that Helicobacter pylori infection induced atherosclerosis in apoe+/- ldlr+/- mice and that Hp-anti-heat-shock protein specific Th1-dominant immune responses had a major involvement in the progression of atherosclerosis. These cellular immune responses caused autoimmunity against endogenous HSP60 (expressed on the stressed cells of vascular endothelium), due to the molecular mimicry. Therefore, an appropriate treatment with antibiotics or with anti-HSP60 antibodies, which regulates the Th1 induction, could sufficiently reduce the progression of atherosclerosis.
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PMID:Chronic infections and atherosclerosis. 1789 24

We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 microg DNA-HSP65. On day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.
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PMID:Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis. 1793 46

Chlamydia pneumoniae, an intracellular microbe, causes respiratory infections and may participate in the development of atherosclerosis. It is able to survive and multiply in macrophages. The susceptibility of monocyte-macrophages from healthy individuals to C. pneumoniae infection in vitro was studied. Intracellular growth of C. pneumoniae, as an indicator of susceptibility to infection, was compared to serum levels of C-reactive protein, soluble CD14 (sCD14), human heat shock protein (HSP)-IgG, human HSP-IgA, C. pneumoniae IgG and IgA antibodies. The production of C. pneumoniae in infected macrophages was highly variable, ranging from 0 to 638 chlamydial genomes per human genome. Chlamydia pneumoniae production associated positively with serum C. pneumoniae IgA (titre: > or =10) and hHSP-IgG and negatively with sCD14 concentration. The association between sCD14 concentration, C. pneumoniae IgA and human HSP-IgG antibodies and C. pneumoniae production was statistically significant only among males. Age and gender did not correlate with the production. We hypothesize that persons whose macrophages cannot restrict the growth of C. pneumoniae are more prone to chronic infection by this agent.
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PMID:Susceptibility of human monocyte-macrophages to Chlamydia pneumoniae infection in vitro is highly variable and associated with levels of soluble CD14 and C. pneumoniae IgA and human HSP-IgG antibodies in serum. 1819 59

Schisandra chinensis (Turcz.) Bail. is often referred to as an example of a medicinal plant with use in modern Chinese medicine. However, Schisandra chinensis first gained recognition as an adaptogen in the official medicine of the USSR in the early 1960s, principally as a result of the large number of pharmacological and clinical studies carried out by Russian scientists in the preceding two decades. Schizandra has now secured an established position within the medicine of Russia/USSR as evidenced by the inclusion of the drug in recent editions of the National Pharmacopoeia of the USSR and in the State Register of Drugs. Pharmacological studies on animals have shown that Schizandra increases physical working capacity and affords a stress-protective effect against a broad spectrum of harmful factors including heat shock, skin burn, cooling, frostbite, immobilisation, swimming under load in an atmosphere with decreased air pressure, aseptic inflammation, irradiation, and heavy metal intoxication. The phytoadaptogen exerts an effect on the central nervous, sympathetic, endocrine, immune, respiratory, cardiovascular, gastrointestinal systems, on the development of experimental atherosclerosis, on blood sugar and acid-base balance, and on uterus myotonic activity. Studies on isolated organs, tissues, cells and enzymes have revealed that Schizandra preparations exhibit strong antioxidant activities and affect smooth muscles, arachidonic acid release, biosynthesis of leukotriene B(4) in leukocytes, platelet activating factor activity, carbohydrate-phosphorus metabolism, the formation of heat shock protein and polyamines, tissue respiration and oxygen consumption, and the tolerance of an organism to oxygen intoxication. In healthy subjects, Schizandra increases endurance and accuracy of movement, mental performance and working capacity, and generates alterations in the basal levels of nitric oxide and cortisol in blood and saliva with subsequent effects on the blood cells, vessels and CNS. Numerous clinical trials have demonstrated the efficiency of Schizandra in asthenia, neuralgic and psychiatric (neurosis, psychogenic depression, astheno-depressive states, schizophrenia and alcoholism) disorders, in impaired visual function, hypotension and cardiotonic disorders, in epidemic waves of influenza, in chronic sinusitis, otitis, neuritis and otosclerosis, in pneumonia, radioprotection of the fetoplacental system of pregnant women, allergic dermatitis, acute gastrointestinal diseases, gastric hyper- and hypo-secretion, chronic gastritis, stomach and duodenal ulcers, wound healing and trophic ulcers. This review describes the considerable diversity of pharmacological effects of Schisandra chinensis reported in numerous studies carried out in the former USSR and which have been confirmed over more than 40 years of use of the plant as an official medicinal remedy. Such knowledge can be applied in the expansion of the use of Schizandra in the pharmacotherapy of European and other countries as well as for the further discovery of new drugs based on the lignans that constitute the main secondary metabolites of this plant.
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PMID:Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. 1851 24

Soluble proteins in aortic smooth muscle cells cultured from atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons were extracted and separated on 2-dimensional electrophoresis gels. Spots were analyzed with Phoretix software and compared between the 2 breeds. Proteins differentially expressed were arrayed on a map, plotting molecular weight against isoelectric point. Eight discrete zones were identified, 5 that included only proteins unique to susceptible cells and 3 that included proteins unique to resistant cells. Of the 88 differentially expressed proteins from susceptible cells, 41 were located in unique zones, whereas 29 of 82 differentially expressed proteins from resistant cells were in unique zones. Selected proteins from susceptibility, and resistance zones were annotated by peptide mass fragments, molecular weights, isoelectric points, and correspondence with genes differentially expressed between cells from the 2 breeds. Some of the annotated proteins (such as smooth muscle myosin phosphatase, myosin heavy chain, fatty acid-binding protein, ribophorin, heat shock protein, and tumor necrosis factor alpha-inducing factor) corresponded to the current hypotheses to explain atherogenesis. In addition, the unique electrophoretic migration zones of proteins associated with susceptibility or resistance should prove useful as a diagnostic tool in clinical settings where species or phenotypes, or both, susceptible or resistant to atherosclerosis can be identified.
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PMID:Differentially expressed soluble proteins in aortic cells from atherosclerosis-susceptible and resistant pigeons. 1857 12

Chlamydophila pneumoniae is a highly prevalent intracellular human pathogen with a unique biphasic life cycle. It is a common cause of upper respiratory infection and pneumonia, and is currently being studied as a potential risk factor for the development of atherosclerotic cardiovascular disease. The outer membrane surface antigens of C. pneumoniae are highly complex: some, such as the major outer membrane protein, are specific, but poorly immunodominant, whereas others have stronger immunogenicity, but are cross-reactive among Chlamydia species. Therefore, new, highly immunodominant, species-specific antigens should be sought. In this regard, the polymorphic membrane proteins (PMPs) are a) unique to Chlamydiae, b) often exposed on the surface of the bacteria, and c) highly immunogenic; these factors make them potential candidates for application in laboratory assays. Other chlamydial antigens, such as heat shock protein (HSP) 60, have been associated with atherosclerotic lesions because of their ability to induce an immunological attack on the endothelial wall. Over the last decade, several studies have suggested a potential role of chronic C. pneumoniae infection in human atherosclerosis. Nevertheless, prospective studies with sufficiently large samples and a healthy comparison group, using a combination of direct and indirect microbiological techniques in the same subject and sample, are needed to establish a relationship between the infection and disease activity.
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PMID:[Chlamydophila pneumoniae: from its proteomics to arteriosclerosis]. 1910 Jan 93

Many reports regarding the cytotoxicity of antibodies to heat shock protein (HSP) 65/60 have implied the potential disadvantage and risk of HSP65/60-specific Th2 shifting strategy in arresting atherosclerosis. In this study, experiments were specifically designed to investigate the effect of a HSP65-specifc Th1 to Th2 immune shift accompanied with high-titer antibodies on atherosclerosis and explore the proatherogenic cytotoxicity of Th2-deviated anti-HSP65 antibodies to endothelial cells. Rabbits were nasally immunized with a fusion protein HSP65-6 x P277 10 times every other day. Immunologic results, including the repressed T-cell proliferation, increased interleukin-10 production and IgG1-predominated isotype of antibodies, revealed a significant Th1 to Th2 shift of response to HSP65. However, rabbits showed no reduction in atherosclerotic lesions. As a control, HSP65 immunization, which induced no antibodies, obviously attenuated atherosclerosis. Further studies on endothelial cells showed that the Th2-deviated anti-HSP65 antibodies could cross-react with HSP60 highly expressed in stressed cells and mediate damage to cells in the presence of complement. In conclusion, the Th2-deviated antibodies to HSP65 that were induced by over-regulated Th2 shift are cytotoxic to endothelial cells. This proatherogenic effect, in contradiction to the positive impact of Th1 suppression, can eventually invalidate the efficacy of Th2 shift in arresting atherosclerosis.
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PMID:A Th2 immune shift to heat shock protein 65 fails to arrest atherosclerosis: Proatherogenic role of Th2-deviated autoantibodies. 1941 13


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