Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes and atherosclerosis have been proposed to be influenced by immune and autoimmune mechanisms. A common incriminated antigen in both disorders is the heat shock protein (HSP)-60/65. In the current study, we established a model combining hyperglycemia with hyperlipidemia in LDL receptor-deficient (LDL-RD) mice and assessed its possible influences on lipid profile, HSP60/65, and atherogenesis. LDL-RD mice were injected either with streptozotocin to induce hyperglycemia or with citrate buffer (control). When hyperglycemia was induced, both study groups were challenged with a high-fat (Western) diet for 6 weeks. Plasma fasting glucose, lipid profile, and antibody levels to HSP65 and oxidized LDL were assessed. At death, the spleens from both groups were evaluated for their proliferative response to HSP65 and the consequent cytokine production. The extent of atherosclerosis was assessed at the aortic sinus. Plasma glucose, cholesterol, and triglyceride levels were elevated in mice injected with streptozotocin compared with control mice. Atherosclerotic lesions were significantly larger in the streptozotocin-injected hyperglycemic LDL-RD mice (132 +/- 23 x 10(5) microm2) in comparison to their normoglycemic litter-mates (20 +/- 6.6 x 10(5) microm2; P < 0.0001). Both humoral and cellular immune response to HSP65 was more pronounced in streptozotocin-injected mice. When challenged with HSP65 in vitro, splenocytes from streptozotocin-injected mice favored the production of the T-helper (TH)-1 cytokine gamma-interferon. In conclusion, we have established a mouse model that combines hyperglycemia with diet-induced hyperlipidemia in LDL-RD mice and studied its effect on atherosclerosis progression. The accelerated atherosclerotic process is associated with heightened immune response to HSP65 and a shift to a TH1 cytokine profile.
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PMID:Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity. 1086 61

The endothelium of the vessel wall as a barrier between blood and the subendothelial matrix proteins is essential for preventing thrombus formation and subsequent atherosclerosis development. Atherosclerosis is an inflammatory disease in which immune and autoimmune mechanisms are involved. Recently, it was demonstrated that endothelial cells in the vessel wall can be damaged not only by classic risk factors, such as hyperlipidemia, smoking and disturbed blood flow, but also (auto)immune reactions to autoantigens present in the cell surface, among which heat shock protein 60 (HSP60) was mostly studied. HSP60 normally located in mitochondria can be translocated into the cell member in response to stress stimuli. Meanwhile, autoantibodies against HSP60 are present in most subjects, especially patients with heart attack and stroke. These autoantibodies may bind to HSP60 expressed in endothelial cells resulting in the cell damage, subsequently initiating the formation of atherosclerotic lesions. Based on the recent progress in the research field, the present review will update the mechanisms of immune response to endothelial cells by which cell damage can initiate the development of atherosclerosis.
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PMID:Immune-mediated mechanisms of endothelial damage in atherosclerosis. 1986 80