Prostacyclin Modulates Cholesteryl Ester Hydrolytic

our previous experiments indicated that smooth muscle cells (SMC) in neointima of injured rabbit aorta (a) acquire the capacity to produce PGI2 and (b) have increased lysosomal CE hydrolytic (acid cholesteryl ester hydrolase [ACEH])activity. Using cultured SMC from rabbit thoracic aorta, we demonstrated that PGI2, 6-keto-PGF1,, and 6-keto-PGE, enhanced ACEH activity fourfold. No significant effects on ACEH activity were observed with PGE1 or PGE2. Preincubation of SMC with an inhibitor of adenylate cyclase activity (dideoxyadenosine) abolished the effect of these PG on CE hydrolytic activity. Addition of dibutyryl cAMP to these SMC significantly increased ACEH activity. Although concentrations of PGI2 used significantly increased cAMP levels, proliferation of these SMC was not observed. In related experiments, we determined if the addition of PGI2, 6-keto-PGF,a, or 6-keto-PGE1 to cultured aortic SMC would enhance the egress of unesterified cholesterol and CE from these SMC. A significant loss of total cholesterol. from PG-treated SMC Parts of this study were presented at a meeting of the Federation of American Societies for Experimental Biology, Atlanta, GA, April 1981. Dr. Hajjar is a recipient of a Senior Investigatorship Award from the New York Heart Association, a Teacher-Scientist Award from the Andrew W. Mellon Foundation, and a National Institutes of Health New Investigator Research Award. Dr. Weksler is a recipient of an American Cancer Society Faculty Research Award. Address reprint requests to Dr. Hajjar, Department of Pathology, Cornell University Medical College, New York 10021. Received for publication 30 April 1982 and in revised form 5 May 1982. was observed at the end of 14 d. Results suggest that increased synthesis of PGI2 by neointimal SMC in the injured aortic wall may, at least in part, explain the changes in CE catabolism and accumulation following injury. These PG may also be important in CE metabolism and accumulation in human arteries.