Arterial prostaglandins and lysosomal function during atherogenesis

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-beta-glucosaminidase, beta-galactosidase (lysosomes); cytochrome oxidase (mitochondria); neutral alpha-glucosidase (endoplasmic reticulum); 5'-nucleotidase (plasma membrane); catalase (peroxisomes)] were compared between control and atherosclerotic preparations. The levels of prostaglandins I2, E2, and F2 alpha, 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 I2 was 10-fold higher than that of prostaglandin E2, which was 3-fold higher than that of prostaglandin F 2 alpha. Prostaglandin I2 doubled in amount with advanced atherosclerosis, while prostaglandin E2 increased over 10-fold, resulting in twice the amount of prostaglandin I2 than E2 in advanced atherosclerosis; the level of prostaglandin F2 alpha did not appear to change significantly with atherosclerosis. Increased levels of prostaglandins I2 and E2 were correlated significantly with increased aortic total cholesterol content (based on DNA) but not increased serum cholesterol levels. N-Acetyl-beta-glucosaminidase activity also was correlated significantly to aortic total cholesterol content and beta-galactosidase activity, as well as to the level of prostaglandin I2; in contrast, N-acetyl-beta-glucosaminidase was not significantly correlated to prostaglandin E2. The association of prostaglandins I2 and E2 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 I2 level and N-acetyl-beta-glucosaminidase activity further suggests a possible role for this prostaglandin during arterial intralysosomal cholesterol accumulation.