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)

Magnetic fields (MFs) from domestic power sources have been implicated as being a potential risk to human health. A number of epidemiological studies have found a significant link between exposure to MFs and increased rates of cancers. There have also been a number of in vivo and in vitro studies reporting effects of MFs in animal disease models and on the expression or activity of a range of proteins. In the past decade, our group proposed that atherosclerosis may have an autoimmune component, with heat shock protein 60 (Hsp60) expressed in endothelial cells as the dominant autoantigen. A number of stressors have been shown to induce the expression of Hsp60, including the classical risk factors for atherosclerosis. We were interested to see if the exposure of endothelial cells to an MF elicited increased expression of Hsp60, as has been reported previously for Hsp70. The present work describes the exposure of endothelial cells to domestic power supply (50 Hz) MFs at an intensity of 700 microT. The results from our system indicate that cultured endothelial cells exposed to a high intensity of MF either alone or in combination with classical heat stress show no effects on the expression of Hsp60 at either the messenger ribonucleic acid or the protein level. As such, there is no evidence that exposure to extremely low-frequency MF would be expected to increase the expression of Hsp60 and therefore the initiation or progression of atherosclerosis.
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PMID:Expression levels of heat shock protein 60 in human endothelial cells in vitro are unaffected by exposure to 50 Hz magnetic fields. 1462 3

The present review focuses on the concept that cellular and humoral immunity to the phylogenetically highly conserved antigen heat shock protein 60 (HSP60) is the initiating mechanism in the earliest stages of atherosclerosis. Subjecting arterial endothelial cells to classical atherosclerosis risk factors leads to the expression of HSP60 that then may serve as a target for pre-existent cross-reactive antimicrobial HSP60 immunity or bona fide autoimmune reactions induced by biochemically altered autologous HSP60. Endothelial cells can also bind microbial or autologous HSP60 via Toll-like receptors, providing another possibility for targetting adaptive or innate immunological effector mechanisms.
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PMID:Autoimmune and inflammatory mechanisms in atherosclerosis. 1503 82

The relative significance of traditional risk factors, chronic infections and autoimmune processes in the development of acute myocardial infarction (AMI) has not been fully elucidated. We compared serum IgG antibody titres to various pathogens, i.e. Chlamydia pneumoniae (Cpn), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), and to the potential autoantigens human heat shock protein 60 (hHSP60) and mycobacterial heat shock protein 65 (mHSP65), in serum samples obtained from patients 3-48 h after AMI (n = 40) or stable effort angina (SEA, n = 43), and from controls (n = 46). The strongest association was observed between AMI and the elevated level of hHSP60 antibodies. The association between AMI and the level of Cpn antibodies was also significant. High levels of hHSP60 and Cpn antibodies represented independent risk factors for the development of AMI, but the simultaneous presence of high levels of antibodies to Cpn and hHSP60 suggested a joint effect on the relative risk of AMI (OR = 12.0-21.1). The antibody titres to mHSP65 were higher in the SEA group than in the controls, and the simultaneous presence of high levels of Cpn and mHSP65 antibodies meant an increased risk among the SEA patients. The antibody titres to CMV or HSV-1 were similar in the three groups. In conclusion, these results demonstrate associations of AMI with high levels of anti-hHSP60 and anti-Cpn antibodies, and of SEA with the level of anti-mHSP65 antibodies, these being independent risk factors.
Atherosclerosis 2004 Apr
PMID:Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease. 1506 11

Individuals with periodontitis have been reported to have a significantly increased risk of developing coronary heart disease. Several studies have demonstrated that the immune response to heat shock protein 60 (HSP60) may be involved in the pathogenesis of both atherosclerosis and chronic periodontitis. To investigate this possible link between these diseases, cellular and humoral immune responses to HSP60 in atherosclerosis patients were compared with those in periodontitis patients and healthy subjects using human and Porphyromonas gingivalis HSP60 (GroEL) as antigens. Antibody levels to both human and P. gingivalis HSP60s were the highest in atherosclerosis patients, followed by periodontitis patients and healthy subjects. Clonal analysis of the T cells clearly demonstrated the presence of not only human HSP60- but also P. gingivalis GroEL-reactive T-cell populations in the peripheral circulation of atherosclerosis patients. Furthermore, these HSP60-reactive T cells seemed to be present in atherosclerotic lesions in some patients. These results suggest that T-cell clones with the same specificity may be involved in the pathogenesis of the different diseases.
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PMID:T-cell clonality to Porphyromonas gingivalis and human heat shock protein 60s in patients with atherosclerosis and periodontitis. 1510 67

The large amount of data accumulated in recent years has reinforced the idea that infectious agents may play a significant role in the pathogenesis of atherosclerosis and in the clinical manifestations of vascular disease. Seroepidemiological and experimental data linking Herpesviridae and Chlamydia pneumoniae to atherosclerosis appear to be confirmed by a number of studies, while the available evidence regarding Helicobacter pylori is more conflicting, partly due to the fact that the interest in this agent is more recent. Infectious agents may influence atherogenesis through a number of mechanisms, ranging from cell lysis to the stimulation of adhesion molecule expression and cytokine production by infected cells. The development of atherosclerosis after an acute infection seems unlikely. Rather, it appears that a chronic, persistent form of infection, especially with Chlamydia pneumoniae, may favor those structural and proinflammatory changes in the vascular wall which are necessary for the formation of an atheroma. A persistent chlamydial infection is accompanied by an increased production of microbial heat shock protein 60, which may induce antigenic mimicry and a chronic inflammatory reaction in the vascular wall. Pharmacological trials have yielded conflicting indications regarding the hypothesis that treatment with macrolide antibiotics may limit the progression of vascular disease and the recurrence of cardiovascular events, although in a limited number of cases. However, antimicrobial drugs do not act specifically against a single infectious agent and more specific therapeutic agents would be needed in order to test a causative link between a single infectious agent and vascular disease.
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PMID:Infectious agents and atherosclerosis: current perspectives and unsolved issues. 1518 98

The heat shock protein 65 kDa (Hsp65) of Mycobacterium tuberculosis var. bovis was fused with the linear polypeptide epitope of cholesteryl ester transfer protein C-terminal fragment (CETPC) and expressed as soluble protein in Escherichia coli. The fusion protein Hsp65-CETPC was purified by anion exchange column and eluted at 100-130 mM NaCl in 10mM phosphate buffer (pH 8.0), and then used to immunize mice via subcutaneous injection or intranasal delivery in the absence of adjuvants. Antibodies against CETPC were detected in immunized mice sera by enzyme-linked immunosorbent assay (ELISA) and verified by Western blot analysis. Specific antibodies were successfully induced and lasted for more than 12 weeks in animals immunized with the fusion protein via both subcutaneous and intranasal routes even in the absence of adjuvants. Results showed that Hsp65 could be used as a convenient carrier molecule for presenting foreign polypeptide epitopes, such as CETPC, to the immune system in vivo. Antibodies induced by Hsp65-CETPC could partially inhibit the excessive activity of CETP to normal level. Therefore, Hsp65-CETPC might be further developed to a vaccine against atherosclerosis.
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PMID:Long-lasting specific antibodies against CETP induced by subcutaneous and mucosal administration of a 26-amino acid CETP epitope carried by heat shock protein 65 kDa in the absence of adjuvants. 1529 73

Atherosclerosis is a vascular disorder involving inflammation, a narrowed vascular lumen in the entire tunica intima, and reduced elasticity of the arterial wall. It has been found that Hsp60 from Chlamydia pneumoniae, an obligate bacterial pathogen associated with atheroma lesions, mimics human Hsp60, thereby causing attacks by immune cells on stressed endothelial cells expressing endogenous Hsp60 on their surface. Furthermore, Hsp60 from C. pneumoniae has been shown to promote the growth of vascular smooth muscle cells (VSMCs). To explore probes that can be used for studying signal transduction elicited by the chlamydial Hsp60, we have tested several natural products for their inhibitory actions on the Hsp60-induced proliferation of rat arterial smooth muscle cells. Sesamol, vanillyl alcohol, and trans-ferulic acid exhibited moderate inhibitory actions on the Hsp60-induced cell proliferation; zerumbone, humulene, and caryophylene effectively inhibited it at low concentrations with IC(50) values of 529, 122, and 110 nM, respectively. The results indicated that the 11-membered alicyclic ring is favorable for interactions with receptors involved in the Hsp60-induced VSMC proliferation.
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PMID:Inhibitory actions of several natural products on proliferation of rat vascular smooth muscle cells induced by Hsp60 from Chlamydia pneumoniae J138. 1545 8

There is accumulating evidence that supports a role of infection in atherosclerosis, with possible mechanism by injuring to the endothelium and inducing an autoimmune response to heat shock proteins (HSPs). In this study, a cDNA array, containing 588 human cardiovascular genes, was utilized to analyze the gene expression profile of Chlamydia pneumoniae (C. pneumoniae) infected human umbilical vein endothelial cells (HUVECs). After 48h of C. pneumoniae infection, the HUVECs were harvested and subjected to immunofluorescent staining, electron microscopy, cDNA array hybridization, RT-PCR, and immunoblotting. This study found a panel of human host genes that were upregulated by C. pneumoniae. The majority of these genes were related to complex lipid metabolism, adhesion receptors, hormones, hormone receptors, and a metalloproteinase that may contribute to atherosclerosis in vivo. Representatives of upregulated gene products, i.e., heat shock protein 60 (HSP60), macrophage scavenger receptor, cytochrome P450, and VEGF165R were immunofluorescently detected in HUVECs, with their greater expression induced by C. pneumoniae infection. These findings supported the opinion that C. pneumoniae might contribute to atherosclerotic development in vivo.
Atherosclerosis 2004 Dec
PMID:Chlamydia pneumoniae (C. pneumoniae) infection upregulates atherosclerosis-related gene expression in human umbilical vein endothelial cells (HUVECs). 1553 Aug 96

Chronic Chlamydia pneumoniae infection and autoimmunity to heat shock protein 60 (Hsp60) have both been documented to be associated with atherosclerosis. Herein, we studied the effects of C. pneumoniae infection and a diet with a low-cholesterol supplement on the development of autoantibodies to mouse Hsp60 and early lipid lesions in the aortic valve of C57BL/6JBom mice. In addition, pulmonary infection was investigated. C57BL/6JBom mice were given one to three C. pneumoniae inoculations and fed either a regular diet or a diet enriched with 0.2% cholesterol. Autoantibody responses against mouse Hsp60 developed in both diet groups when the mice were infected with C. pneumoniae and in uninfected mice fed a cholesterol-enriched diet. C. pneumoniae infections increased subendothelial foam cell accumulation in mice on a 0.2% cholesterol-enriched diet (p = 0.022), without apparent hypercholesterolemia. These in vivo data suggest that autoantibodies against mouse Hsp60 develop as a consequence of cholesterol feeding and repeated C. pneumoniae infections. Further, infectious burden increased early lipid lesions in C57BL/6JBom mice fed a cholesterol-enriched diet.
Atherosclerosis 2004 Dec
PMID:Heat shock protein 60 autoimmunity and early lipid lesions in cholesterol-fed C57BL/6JBom mice during Chlamydia pneumoniae infection. 1553 Sep 6

Numerous studies have identified a role for the innate and adaptive immune response in atherosclerosis; both pro- and antiatherogenic roles for the immune responses have been demonstrated. Common autoantigens against which an immune response has been identified in experimental and human models of atherosclerosis include oxidized low-density lipopoteins, beta2 glycoprotein 1 and heat shock protein 60. Activation of atheroprotective adaptive immune responses have been demonstrated for oxidized low-density lipoprotein-related antigens. Conversely, atheroprotection has been demonstrated with the induction of immune tolerance through activation of mucosal immunity to heat shock protein 65/60 and beta2 glycoprotein 1. Recent identification of specific immunoreactive antigenic epitopes in the apolipoprotein B-100 component of low density lipoproetin and early experimental observations have provided proof of concept that active vaccination using specific apolipoprotein B-100-related antigens may emerge as a novel immunomodulating atheroprotective strategy.
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PMID:Vaccination for atherosclerosis: a novel therapeutic paradigm. 1560 56


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