| Atherosclerosis is one of the main diseases endangering human's healthiness. The researches in mechanisms of atherosclerosis are hotspot in the field of cardiovascular disease. A great deal researches indicated that atherosclerosis resulted from interaction of multiple factors, i.e. abnormality of lipid metabolism, blood coagulation factors, cytokines, hemodynamics loading, heredity, risk factors of behaviors and potential infection. The basis pathologic atherosclerotic lesion represented a series of highly specific cellular and molecular responses that can best be described as an chronic inflammatory disease. The earliest type of lesion, the so-called fatty streak, was a pure inflammatory lesion, consisting only of monocyte-derived macrophages and T lymphocytes.CD40, a 49-kDa transmembrane glycoprotein, expresses on many kinds of cells including B lymphocyte, monocyte, fibroblast and endothelial cell. The interaction between CD40 and its ligand (CD40L) is not only confined in signal convection in inflammatory cell, but also involve in the regulation of inflammatory reaction of main cells in atherosclerosis. Nevertheless the mechanisms of higher-level regulation of CD40 and CD40L are still unclear.Peroxisome proliferator-activated receptor-gamma ( PPAR Y ) , a nuclear receptor, extensively expressed on many types of cells (including monocyte/macrophage) and tissues such as atherosclerotic focus, is related to transcription regulation of a lot of substance. It may be concerned with the inflammatory modulation. So far there is no report of whether it modulates the transcription of CD40.By detecting the changes of CD40, CD40L and PPAR Y expression levels in atherosclerotic animal model, monocytes stimulated by ligands or antibodies, and acute coronary events induced by the plaque rupture, this study try to discuss the regulation of CD40/CD40L by PPAR Y and the effect of some drugs, aimed at finding some clues in the treatment of atherosclerosis.METHODS: (1) Experimental atherosclerotic animal model of rats by using cholesterol-rich diet and large dosage of vitamin D were as AS group, the rats fed general diet as control group. Simvastatin and rosiglitazone-PPAR Y agonist, one of thiazolidinediones(TZDs) were used in anther two drug interfering groups (10 rats ineach group). Drawing blood from rats' heart for testing serum lipids. Aortas were dissected for HE staining, electron microscope studying and immunohistochemistry studying. The macrophages of rats enterocoelia in each group were collected to detect the expression of CD40, CD40L and PPAR y mRNA through reverse transcriptase polymerase chain reaction (RT-PCR) with P -actin as inner control. (2) Culturing human monocyte line-U937 with which to assay the expression of CD40 and PPAR Y by stimulating cells with PPAR Y agonist 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), anti-PPARY polyclonal antibody (PPARyAb), recombination human CD40L(rCD40L) and anti-CD40 polyclonal antibody (CD40Ab) respectively. Observing the expression of cellular PPAR Y and CD40 protein level through Western Blot. (3) Selected coronary heart disease (CHD) patients and classified them into stable angina pectoris group (SAP), unstable angina pectoris group (UAP) and acute myocardial infarction group (AMI). Patients with no CHD were as control group (CON), 20 patients in each group. Collected their data of blood examinations, and detected the expression of CD40/CD40Ls PPAR Y mRNA by RT-PCR in their monocytes separated from circulating blood.RESULTS: (1) The level of rats serum lipids (total cholesterol and LDL-C) of AS group was higher significantly than that of simvastatin and rosiglitazone groups, and thats of these three groups were higher significantly than the control group. (2) In AS group, the obviously proliferation and chaotic arrangement of aorta smooth muscle cells, obscure elastic fibrous layer and fibrous plaque extruding towards lumen were observed light-microscopically. Distorting endothelial cell nuclear and proliferation of collagen fibers underlying endothelium...
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