文章基本信息

标题：Retinoic acid induces PGI synthase expression in human endothelial cells
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作者：Mercedes Camacho ; Cristina Rodríguez ; Juliana Salazar 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：8
页码：1707-1714
DOI：10.1194/jlr.M700559-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Retinoic acid (RA) exhibits anti-inflammatory, anti-tumor, and immuno-modulatory actions, and affects angiogenesis and thrombosis. Arachidonic acid (AA) metabolites are involved in all these processes. We explored the effect of RA on AA metabolism in human umbilical vein endothelial cells (HUVECs). 13- cis -RA increased the release of prostaglandin I₂ (PGI₂₎, both spontaneous and thrombin-induced, in terms of 6-oxo-PGF_1α analyzed by enzyme-immunoassay. Coincubation with 13- cis -RA and interleukin-1β resulted in a synergic increase in the release of PGI₂. Consistently, 13- cis -RA increased the ability of HUVECs to inhibit AA-induced platelet aggregation. 13- cis -RA did not induce cyclooxygenase-isoenzyme expression, determined by immunoblotting, or activity, evaluated by analyzing eicosanoids formed from exogenous labeled AA by HPLC. In contrast, RA induced PGI synthase (PGIS) activity and expression in terms of mRNA and protein determined by real-time PCR and Western blotting, respectively. Results from experiments with several species of RA and with retinoic acid receptor (RAR) and retinoid X receptor (RXR) antagonists showed that the effect of RA on PGIS expression was mediated by RAR. Actinomycin D and cycloheximide both inhibited RA-induced PGIS expression. Furthermore, RA increased PGIS transcriptional activity in transient transfection assays, an effect that was prevented by an RAR antagonist. These results reinforce the concept that RA could be beneficial for patients with cardiovascular risk.