Arterial prostaglandins and lysosomal function during atherogenesis: I. Homogenates of Diet-induced Atherosclerotic Aortas of Rabbit

Abstract

Homogenates of control and diet-induced atherosclerotic aortas of rabbit were prepared and the levels of DNA, protein, free and esterified cholesterol, and six enzymes known to be associated with various subcellular organelles [ N-acetyl-β-glucosaminidase, β-galactosidase ( lysosomes); cytochrome oxidase ( mitochondria); neutral α-glucosidase ( endoplasmic reticulum); 5′-nucleotidase ( plasma membrane); catalase ( peroxisomes)] were compared between control and atherosclerotic preparations. The levels of prostaglandins I 2, E 2, and F 2α, based on DNA, also were measured by radioimmunoassay. Atherosclerotic aortas were significantly enriched in catalase activity (440%) and in each of the acid hydrolases (395 and 630%), based on DNA, as well as in free (630%) and esterified cholesterol (930%), based on tissue wet weight, compared to control aortas. The control level of prostaglandin I 2 was 10-fold higher than that of prostaglandin E 2, which was 3-fold higher than that of prostaglandin F 2α. Prostaglandin I 2 doubled in amount with advanced atherosclerosis, while prostaglandin E 2 increased over 10-fold, resulting in twice the amount of prostaglandin I 2 than E 2 in advanced atherosclerosis; the level of prostaglandin F 2α did not appear to change significantly with atherosclerosis. Increased levels of prostaglandins I 2 and E 2 were correlated significantly with increased aortic total cholesterol content (based on DNA) but not increased serum cholesterol levels. N-Acetyl-β-glucosaminidase activity also was correlated significantly to aortic total cholesterol content and β-galactosidase activity, as well as to the level of prostaglandin I 2; in contrast, N-acetyl-β-glucosaminidase was not significantly correlated to prostaglandin E 2. The association of prostaglandins I 2 and E 2 with aortic total cholesterol suggests the participation of prostaglandins in the response of arterial cells to lipid accumulation in atherosclerosis. The specific association of aortic prostaglandin I 2 level and N-acetyl-β-glucosaminidase activity further suggests a possible role for this prostaglandin during arterial intralysosomal cholesterol accumulation.