Pomerantz K B, Hajjar D P
Department of Medicine, National Institutes of Health Specialized Center of Research in Thrombosis, Cornell University Medical College, New York, New York 10021.
Biochemistry. 1990 Feb 20;29(7):1892-9. doi: 10.1021/bi00459a033.
Eicosanoids have been implicated in the regulation of arterial smooth muscle cell (SMC) cholesteryl ester (CE) metabolism. These eicosanoids, which include prostacyclin (PGI2), stimulate CE hydrolytic activities. High-density lipoproteins (HDL), which promote cholesterol efflux, also stimulate PGI2 production, suggesting that HDL-induced cholesterol efflux is modulated by eicosanoid biosynthesis. To ascertain the role of endogenously synthesized eicosanoids produced by arterial smooth muscle cells in the regulation of CE metabolism, we examined the effects of cyclooxygenase inhibition on CE hydrolytic enzyme activities, cholesterol efflux, and cholesterol content in normal SMC and SMC-derived foam cells following exposure to HDL and another cholesterol acceptor protein, serum albumin. Alterations of these activities were correlated with cholesterol efflux in response to HDL or bovine serum albumin (BSA) in the presence or absence of aspirin. HDL stimulated PGI2 synthesis and CE hydrolases in a dose-dependent manner. Eicosanoid dependency was established by demonstrating that HDL-induced acid cholesteryl ester hydrolase (ACEH) activity was blocked by aspirin. CE enrichment essentially abrogated HDL-induced PGI2 production in cells which also exhibited decreased lysosomal and cytoplasmic CE hydrolase activities. In CE-enriched cells whose cytoplasmic CE pool was metabolically labeled with [3H]oleate or cLDL containing [3H]cholesteryl linoleate, aspirin did not alter HDL- or BSA-induced net CE hydrolysis or efflux, respectively. Finally, aspirin treatment did not alter the mass of either free or esterified cholesterol content of untreated or CE-enriched SMC following exposure to acceptor proteins. These data demonstrated that CE enrichment significantly reduced HDL-induced activation of CE hydrolytic activity via inhibition of endogenous PGI2 production.(ABSTRACT TRUNCATED AT 250 WORDS)
类二十烷酸与动脉平滑肌细胞（SMC）胆固醇酯（CE）代谢的调节有关。这些类二十烷酸，包括前列环素（PGI2），可刺激CE水解活性。促进胆固醇流出的高密度脂蛋白（HDL）也能刺激PGI2的产生，这表明HDL诱导的胆固醇流出受类二十烷酸生物合成的调节。为了确定动脉平滑肌细胞内源性合成的类二十烷酸在CE代谢调节中的作用，我们研究了环氧化酶抑制对正常SMC和SMC来源的泡沫细胞在暴露于HDL和另一种胆固醇受体蛋白血清白蛋白后CE水解酶活性、胆固醇流出和胆固醇含量的影响。这些活性的改变与在有或没有阿司匹林的情况下对HDL或牛血清白蛋白（BSA）的胆固醇流出相关。HDL以剂量依赖的方式刺激PGI2合成和CE水解酶。通过证明HDL诱导的酸性胆固醇酯水解酶（ACEH）活性被阿司匹林阻断，确定了类二十烷酸的依赖性。CE富集基本上消除了细胞中HDL诱导的PGI2产生，这些细胞的溶酶体和细胞质CE水解酶活性也降低。在细胞质CE池用[3H]油酸或含有[3H]胆固醇亚油酸酯的cLDL进行代谢标记的CE富集细胞中，阿司匹林分别没有改变HDL或BSA诱导的净CE水解或流出。最后，阿司匹林处理在暴露于受体蛋白后没有改变未处理或CE富集的SMC中游离或酯化胆固醇含量的质量。这些数据表明，CE富集通过抑制内源性PGI2产生显著降低了HDL诱导的CE水解活性激活。（摘要截短至250字）
