Chronic renal failure accelerates atherogenesis in apolipoprotein E-deficient mice

Area of Science:

• Nephrology
• Cardiovascular Medicine
• Atherosclerosis Research

Background:

• Cardiovascular mortality is significantly elevated in patients with chronic renal failure (CRF).
• Atherosclerosis pathogenesis in CRF is not fully understood despite abundant risk factors.
• Apolipoprotein E-deficient mice are a valuable model for studying atherosclerosis.

Purpose of the Study:

• To investigate the effect of chronic renal failure (CRF) on the development of atherosclerosis.
• To utilize the apolipoprotein E-deficient mouse model to examine uremia-accelerated atherogenesis.
• To identify predictors of accelerated atherosclerosis in the context of CRF.

Main Methods:

• Apolipoprotein E-deficient male mice underwent 5/6 nephrectomy (CRF), unilateral nephrectomy (UNX), or no surgery.
• Aortic plaque area, cholesterol content, and root plaque area were quantified 22 weeks post-surgery.
• Plasma urea, cholesterol, and homocysteine levels, along with blood pressure, were measured.

Main Results:

• CRF mice exhibited significantly increased aortic plaque area, cholesterol content, and aortic root plaque area compared to controls.
• Plaques in uremic mice contained CD11b-positive macrophages and showed nitrotyrosine staining.
• Plasma urea levels strongly correlated with and were a significant predictor of aortic plaque area fraction.

Conclusions:

• Uremia markedly accelerates atherogenesis in apolipoprotein E-deficient mice.
• The accelerated atherosclerosis in CRF is not fully explained by changes in blood pressure, homocysteine, or total cholesterol.
• The CRF apolipoprotein E-deficient mouse serves as a novel model for studying the pathogenesis of accelerated atherosclerosis in uremia.