Triphasic response of prostacyclin production in rabbit thoracic aorta in early atherosclerosis

Abstract

Atherosclerosis was induced in male rabbits by administration of a 2% cholesterol diet for up to 18 weeks. The animals were 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 PGI 2 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 PGI 2 synthesis with the development of early atherosclerosis. Phase one is a fall in aortic PGI 2 synthesis which predates the appearance of plaque. In phase 2, a significant rise in aortic PGI 2 with the appearance of plaque could represent compensation of aortic endothelium to prevent further plaque development. In phase 3, decreased aortic PGI 2 could indicate replacement of normal endothelium by atherosclerotic plaque.