Atherosclerosis And Stroke Pathogenesis Of Matrix Metalloproteinases, Cox-2 And Atherosclerosis Occur, Related To The Development

Background Atherosclerosis has been linked to inappropriate vascular remodeling, which may result from the accumulation of inflammatory cells and the increased deposition of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2) have been proposed to participate in these pathological processes. This study was to investigate MMP-2, its specific regulators-membrane type (MT) 1-MMP and tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), MMP-3, TIMP-3, and COX-2, the status of internal elastic lamina, as well as collagen content in atherogenesis in a cholesterol-fed rabbit model, and whether inhibition of COX-2, by selective inhibitor, DFU [5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)-phenyl-2-(5H)-furanone], could block the progression of atherosclerosis. Methods1.Animal model.46 New Zealand White Rabbit (NZW) (six weeks old) were fed a high lipid diet containing 2% cholesterol and 3% lard. Six rabbits were euthanized at day 0, then 8 after every 2 weeks till total 10 weeks. Fasted plasma lipid parameters before and after high lipid diet were measured. Aortic arch was excised and subjected to histological examination (including HE staining, Sudan IV staining, Sirius Red staining and Verhoeff-van Gieson' s staining), immunohistochemistry for macrophage, smooth muscle cell, COX-2, MMPs and TIMPs, and in situ zymography for gelatinases and caseinases. Pathological classification of atherosclerosis in aorta was performed...