Aortic constriction exacerbates atherosclerosis and induces cardiac dysfunction in mice lacking apolipoprotein E.
Despite considerable evidence suggesting that hypertension contributes to the development and progression of atherosclerosis, the causative links remain unclear. We have tested the effects of chronic hypertension induced by suprarenal aortic constriction on the development of atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. Compared with a sham operation, narrowing the aortic luminal diameter by 33% increased blood pressure proximal to the constriction by approximately 15 mm Hg, but the pressures distal to the constriction were unchanged. Kidney renin mRNA and plasma renin activity were also unaffected. Compared with plaque size after the sham operation, atherosclerotic plaque size in the aortic root 8 weeks after coarctation was increased to 245% and 152% in males and females, respectively. Aortic segments at the constriction were free of atherosclerotic deposits, but segments proximal to the constriction were dilated and had atherosclerotic lesions. Thrombi were present immediately below the constriction in Apoe-/- and wild-type vessels. Surprisingly, compared with wild-type mice, the Apoe-/- mice were more susceptible to the cardiac hypertrophy and dysfunction induced by pressure overload. Thus, aortic coarctation exacerbates atherosclerosis in vessels proximal to the constriction without a concomitant increase in the renin-angiotensin system. Our study also suggests that apolipoprotein E plays an important role in modulating cardiac hypertrophy.
Wu
Jiao-Hui
JH
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill 27599-7525, USA.
Hagaman
John
J
Kim
Shinja
S
Reddick
Robert L
RL
Maeda
Nobuyo
N
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology; D001018:Aortic Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D001794:Blood Pressure; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D003250:Constriction; D018450:Disease Progression; D005260:Female; D006973:Hypertension / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016019:Survival Analysis; D014463:Ultrasonography
D001057:Apolipoproteins E