期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 32, 期 10, 页码 2372-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.111.236158
关键词
animal model; plaque rupture; thrombus; mechanical stress; angiotensin
资金
- National Natural Science Foundation [30971185, 81070239, 81170192]
- Shanghai Municipal Natural Science Foundation [09JC1409400, 10JC1409400, 11JC1407100, 10410701200]
- US Army Medical Research and Material [BC103870]
Objective-The development of a murine model of spontaneous atherosclerotic plaque rupture with luminal thrombus. Methods and Results-Combined partial ligation of the left renal artery and left common carotid artery in 8-week-old apolipoprotein E-deficient mice induced endogenous renovascular hypertension and local low oscillatory shear stress in the left common carotid artery. After 8 weeks, a fresh left common carotid artery lumen thrombus associated with severe plaque burden was found in 50% (10/20) of the mice. Histological analyses indicated that all left common carotid artery lesions had vulnerable features, and 50% (5/10) of the mice showed plaque rupture with a lumen thrombus. Multiple layers with layering discontinuity and intraplaque hemorrhages were found in 80% (8/10) of the mice. Further experiments showed that both increased blood pressure, and angiotensin-II contributed to plaque progression and vulnerability. Decreased intimal collagen associated with increased collagenase activity and matrix metalloproteinase expression also resulted in plaque disruption. Conclusion-We demonstrate a murine model of spontaneous plaque rupture with a high incidence of luminal thrombus. The model not only nicely recapitulates the pathophysiological processes of human plaque rupture but it is also simple, fast, and highly efficient to generate. (Arterioscler Thromb Vasc Biol. 2012; 32: 2372-2379.)
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