| Clinical trials demonstrated that the vast majority of acute coronary events arise fromatherosclerotic lesions that are minimal to moderate in severity as quanified byateriography. Coronary plaque ruptllre plays an impoftam role in acllte coronarysyndromes. Pathological studies show that the vulnerable p1aque are rich inmonocyte-derived macrophages, which tum into foam cells and contribute to lipid-ladenplaque; release proteolytic enzymes that degrade extracellular matrix and weaken a thinoverlying flbrous caPs, precipitating plaque disruPtion. CD36, a multifiinctional receptof,acts both as adhesion molecule and as scavenger receptor It may contributes to monocyteadhesion to the endothelium and fOam cells fOrmation. Peroxisome proliferators-activatedreceptor gamma (PPARY) is the member of PPARs subfamily of the nuclear receptor genefamily. It is a ligand-dependent transcription factor. It is also the molecular target of insulinaction enhancer. PPARY is not only take aPart in the regulation of lipid and glucosemetabolism, adipocyte differentiation and lipid homeostasis, but also the importanmedium of inflaxnmation. It affects the development of atherosclerosis and the stability of' plaque through several aPproaches. The promoter regions of CD36 contains sequence thatcan be binded by PPARY. PPARY is 1ikely to induce monocyte/macrophage expressingCD36 through transcriptional regulation after activated by ligand, Which increases theuptake of lipid. So PPARY maybe is the sign of atherosclerotic lesion, as well as a newtheraPy target of insulin resistance and cardiovascular events.To gain insight of the roles and the mutuality of the tWo receptor in the development ofvulnerable plaque and the influence of statin, in situ hybridization andirnmunohistochemical staining were aPplied to observe the expression of CD36 and PPARin atherosclerotic plaque though experimental animal models of homoZygous mice.Adhesion experimeni, electTon microscope technique and westem blot were also used toinvestigate the changes of the two receptors dUring the process of monocyte adhesion toendothelium cell, and the monocyte turning into fOam cell after lipid over uPtaken. Inaddition, flow cytometry and RTPCR were aPplied to meastire the expression levels ofthe two receptors in patients suffering acute coronary syndromes.The main contcnts and resultsl. EstabIishment of experimentaI atherosclerotic animaI models of homoZygous mice.Adult homozygous mice C57BL/6 were fed a cholesterol-rich diet with vitamin D2 addedfor l4 weeks. After l4 weeks, all the mice were fed general diet for another 8 weeks. Atthe same time, the atherosclerotic mice were divided into 3 grouPs, two of them receivedthe diet together with Pravastatin(ST grouP, 10mg/kg/d) or Pioglitazon(PIO grouP,l0mg/kg/d) as the medicine interfered grouP, one of them received the diet only asatherosclerotic control grouP(AS grouP). The other group was fed general diet from thevery beginning as the normal control group(CON group). Weight, lipid, glucose andinsulin levels were observed. aortas were dissected in different stage(0, the end of 4th, 8th,l4th and 22nd week). The histopathological changes were observed by oil red O staining.The exPressions of CD36 and PPARY were detected by in sAn hybridization andinununohistochemical staining. The weight and the levels of lipid, glucose and insulin ofcholesterol-rich fed mice were increased gradually during the first l4 weeks, Whereas theweight decreased after 12 weeks. The levels of lipid, glucose and insulin dropped aftersuccedent 8 weeks of general diet together with medicines. The oil red O staindemonstrated that the aortic endothecium taken at the end of the 8th and 14th week werestained red locally. Immunohistochemical staining demonstrated there were stainedpositively brown in the aortic lesions in AS grouP. There were significanly less positivestain in both medicine interfered groups. In CON group th... |
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