Prostacyclin-mediated effect of high density lipoproteins as cellular cholesterol acceptors on aortic smooth muscle cells

Abstract

Low (LDL) and high (HDL) density lipoproteins stimulate prostacyclin (PGI 2) synthesis in cultured rabbit and human aortic smooth muscle cells. In this respect, the efficacy of HDL exceeded that of LDL, HDL 3 being the most effective. HDL 3 obtained from hypoalphacholesterolemic patients' serum had a lesser stimulative effect on PGI 2 synthesis as compared with HDL 3 of normolipidemic subjects. Partially purified apoprotein A-1 stimulates the metabolism of 14C-arachidonic acid accompanied with enhanced formation of prostaglandins, especially 6-keto-PGI 1α. Within a 24 h incubation in the fetal calf serum-free medium, prostaglandins I 2 and E 1 (1 × 10 −7 m) reduce the intracellular cholesterol level in human aortic smooth muscle cells by 30%. Total HDL fraction as well as HDL 3 and HDL 2b applied in combination with prostaglandins have a synergistic effect resulting in a 50% fall in intracellular cholesterol. Hypothetically, the uptake of cholesterol by HDL may include the following stages: (1) HDL interacts with the cell and activates the intracellular PGI 2 synthesis probably via apo A-1 modulatory action on arachidonic acid metabolism; (2) newly synthesized PGI 2 activates cholesteryl ester hydrolase leading to the formation of free cholesterol; (3) HDL takes up free cholesterol.