Endogenous Renovascular Hypertension Combined With Low Shear Stress Induces Plaque Rupture in Apolipoprotein E–Deficient Mice
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.
- Received August 4, 2011.
- Accepted August 3, 2012.
- © 2012 American Heart Association, Inc.