Aortic Microsomal Prostacyclin Synthesis During Diet Induced Hypercholesterolemia

Abstract

Atherosclerosis was induced in male rabbits with administration of a 2% cholesterol diet up to 18 weeks and assessed for aortic microsomal prostanoid synthesis, morphologic assessment and serum cholesterol levels. Serum levels of cholesterol increased from control values of 84±9 ng/dl to 1632±227 ng/dl at 2 weeks (20 fold increase), and 4859±829 ng/dl at 9 weeks (57 fold increase). Aortic microsomal prostacyclin synthesis fell significantly at 2 weeks of cholesterol feeding which, predated the morphologic appearance of atherosclerotic plaque in the 7 week group. Aortic microsomal PGI2 synthesis significantly increased by 7 weeks and did not fall until the 18 week group when a highly significant increase in aortic plaque developed. These findings suggest a triphasic response of aortic PGI2 synthesis with the development of early atherosclerosis. Phase one is a fall in aortic PGI2 synthesis which predates the appearance of plaque. In phase 2, a significant rise in aortic PGI2 with the appearance of plaque could represent compensation of aortic endothelium to prevent further plaque development. In phase 3, decreased aortic PGI2 could indicate replacement of normal endothelium by atherosclerotic plaque. Aortic microsomes prepared from the female rabbits fed a cholesterol enriched diet up to 12 weeks demonstrated results similar to the male groups.