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Published on: January 13, 2012
Aortic constriction exacerbates atherosclerosis and induces cardiac dysfunction in mice lacking apolipoprotein E
Jiao-Hui Wu1, John Hagaman, Shinja Kim
1Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill 27599-7525, USA.
Insights
Chronic hypertension induced by aortic constriction significantly worsens atherosclerosis in mice lacking apolipoprotein E (Apoe-/-). This exacerbation occurs without activating the renin-angiotensin system, highlighting hypertension
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Hypertension Studies
Background:
- Hypertension is a known risk factor for atherosclerosis development and progression.
- The precise causal mechanisms linking hypertension to atherosclerosis remain incompletely understood.
- Apolipoprotein E deficiency (Apoe-/-) is a model for accelerated atherosclerosis.
Purpose of the Study:
- To investigate the impact of experimentally induced chronic hypertension on atherosclerosis.
- To determine the role of aortic coarctation in exacerbating atherosclerotic plaque formation.
- To assess the influence of apolipoprotein E on cardiac response to pressure overload.
Main Methods:
- Induction of chronic hypertension via suprarenal aortic constriction in apolipoprotein E-deficient (Apoe-/-) mice.
- Comparison of atherosclerotic plaque size and distribution between hypertensive and sham-operated control groups.
- Measurement of blood pressure, kidney renin mRNA, plasma renin activity, and assessment of cardiac hypertrophy and dysfunction.
Main Results:
- Aortic constriction significantly increased blood pressure proximal to the constriction.
- Atherosclerotic plaque size in the aortic root increased substantially (245% in males, 152% in females) in hypertensive Apoe-/- mice.
- Apoe-/- mice exhibited greater susceptibility to cardiac hypertrophy and dysfunction compared to wild-type mice under pressure overload.
Conclusions:
- Aortic coarctation exacerbates atherosclerosis in vessels proximal to the constriction, independent of renin-angiotensin system activation.
- Hypertension plays a direct role in promoting atherosclerotic lesion development.
- Apolipoprotein E is crucial in modulating the cardiac response to pressure-induced overload.
Abstract:
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.
