Aortic constriction exacerbates atherosclerosis and induces cardiac dysfunction in mice lacking apolipoprotein E.

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.