Metabolic activity of cholesteryl esters in aortic smooth muscle cells is altered by prostaglandins I2 and E2.
Among the biochemical processes associated with the atherogenic process are increased aortic cholesteryl ester (CE) accumulation and altered prostaglandin (PG) production. The precise physiological role of PG, particularly prostacyclin (PGI2), in the control of CE metabolism in intact aortic smooth muscle cells remains to be fully elucidated. We report here that cytosolic neutral cholesteryl ester hydrolytic activity (NCEH) in intact cultured aortic smooth muscle cells is significantly increased by 75-250 nM PGI2 at the end of a 2-hr incubation period. The effect was mediated by increased intracellular cAMP levels since the effect of PGI2 on NCEH activity was abolished in the presence of an inhibitor of adenylate cyclase activity, viz., dideoxyadenosine (DDA0. Although the addition of 20-100 microM dibutyryl cAMP (Bt2cAMP) and 50-100 microM sodium arachidonate also increased NCEH activity twofold, 6-keto PGF1 alpha, PGE1, and PGE2 did not increase the activity of this enzyme. In contrast to these findings, 75-250 nM PGE2 significantly inhibited CE synthetic activity (ACAT) approximately 60%. Arachidonate or Bt2cAMP did not affect ACAT activity. This decrease in ACAT activity induced by PGE2 does not appear to be mediated by cAMP. Taken together, these findings suggest that PGI2, a well known potent vasodilator and inhibitor of platelet aggregation, and PGE2 may have an important regulatory role in aortic CE metabolism.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism*; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D011817:Rabbits; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D002788:Cholesterol Esters; D011458:Prostaglandins E; D003994:Bucladesine; D011464:Epoprostenol; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase; D015232:Dinoprostone