Hypertension and endothelial dysfunction in apolipoprotein E knockout mice

Area of Science:

• Cardiovascular Science
• Animal Models of Disease
• Pharmacology

Background:

• Mice lacking apolipoprotein E (ApoE) are a model for studying hypercholesterolemia and atherosclerosis.
• Atherosclerosis progression is associated with hemodynamic changes and endothelial dysfunction.

Purpose of the Study:

• To investigate hemodynamics and endothelial function in ApoE-deficient mice at different stages of disease.
• To determine the role of atherosclerosis in hypertension and endothelial dysfunction.

Main Methods:

• Hemodynamic measurements (arterial pressure, cardiac remodeling) and histopathological analysis of renal arteries were performed in 6-week-old and 7.5-month-old Apoe(-/-) mice and controls.
• Endothelial function was assessed by measuring cutaneous blood perfusion changes in response to nitric oxide-mediated (mustard oil) and cyclic adenosine monophosphate-mediated (cilostazol) vasodilation.

Main Results:

• 7.5-month-old Apoe(-/-) mice exhibited hypertension, cardiac remodeling, renal artery atherosclerosis, and blunted nitric oxide-mediated vasodilation compared to controls.
• 6-week-old Apoe(-/-) mice, with hypercholesterolemia but no atherosclerosis, showed normal hemodynamics and endothelial function.
• Cilostazol-induced vasodilation was preserved in 7.5-month-old Apoe(-/-) mice, suggesting specific impairment of nitric oxide pathways.

Conclusions:

• Hypertension and endothelial dysfunction in advanced ApoE-deficient atherosclerosis are primarily driven by the atherosclerotic process.
• Nitric oxide-mediated vasodilation is compromised in the presence of significant atherosclerosis.
• Early hypercholesterolemia alone does not induce significant hypertension or endothelial dysfunction in this model.