Atherosclerosis in uremic mice

To study the possibility that susceptibility to the development of atherosclerosis during chronic renal failure is genetically determined, aortic lesion formation and changes in serum lipid levels in mice of 2 different inbred strains, C57BL/6J and A/J, were examined. Chronic uremia was induced by electrocoagulation of the right renal cortex and left nephrectomy. The mice were then fed either normal rodent chow or a saturated fat and cholesterol-enriched diet for 6 weeks. None of the A/J mice developed atherosclerosis, whereas the aortas of chow-fed uremic C57BL/6J mice were found to contain a number of fatty lesions, the severity of which was increased by a high fat diet. Uremia had different effects on serum cholesterol, triglycerides, and lipoproteins in the two strains. The results suggest that the resistance of A/J mice to uremia-induced atherosclerosis may be attributed to their ability to maintain high serum HDL-cholesterol levels and/or low serum triglyceride levels. The results further indicate that the development of atherosclerotic lesions in uremic mice is both genetically determined and affected by diet.