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.


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.


CONCLUSIONS
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.
Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shu-xuan
SX
Jin
Ling-hong
LH
Shen
Peng
P
Nie
Wei
W
Yuan
Liu-hua
LH
Hu
Dan-dan
DD
Li
Xue-jin
XJ
Chen
Xiao-kun
XK
Zhang
Ben
B
He
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001794:Blood Pressure / Q000502:physiology; D002340:Carotid Artery Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D017536:Carotid Artery, Common / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D015994:Incidence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013314:Stress, Mechanical
D001057:Apolipoproteins E; D000804:Angiotensin II; D003094:Collagen; D017364:Collagenases