title: Clopidogrel reduces apoptosis and promotes proliferation of human vascular endothelial cells induced by palmitic acid via suppression of the long non-coding RNA HIF1A-AS1 in vitro.
abstract: Cardiovascular disease (CVD) is recognized as a major and increasing health problem affected older subjects in China, and clopidogrel has been widely used for treatment of CVD patients such as atherosclerosis, myocardial infarction, and myocardial ischaemia-reperfusion damage. However, the molecular mechanisms of clopidogrel for treatment of CVD are only partially understood. This study investigated the effects of clopidogrel on palmitic acid-induced damage of human vascular endothelial cells (HUVECs), and the molecular mechanisms of LncRNA HIF1A-AS1 in regulating the proliferation and apoptosis of HUVECs in vitro. We firstly established a damage model of HUVECs through palmitic acid (PA) treatment. And the effect of clopidogrel reducing PA-induced apoptosis of HUVECs was observed by the flow cytometric measurement. To further understand the molecular mechanism of clopidogrel rescues PA-induced apoptosis, we used human LncRNA PCR array to compare the LncRNA expression profile difference between clopidogrel-treated cells and control cells. The expression of LncRNA HIF 1 alpha-antisense RNA 1 (HIF1A-AS1) was significantly altered in clopidogrel-treated cells. We further proved that suppression of HIF1A-AS1 by siRNA reduce PA-induced apoptosis and promote proliferation of HUVECs. Furthermore, we also demonstrated inhibition apoptosis effect by HIF1A-AS1 is related to mitochondrial apoptosis pathway. Hence, our results suggest that clopidogrel rescues apoptosis and promotes proliferation of PA-induced damage model of HUVECs through inhibiting the mediator LncRNA HIF1A-AS1. These findings indicate that LncRNA HIF1A-AS1 may play an important role in the pathogenesis of CVD, and provide a novel molecular mechanism of clopidogrel for treatment of CVD.
authors.affiliation: Department of Rheumatology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Chen
authors.forename: Hongfei
authors.initials: H
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Gong
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Xueling
authors.initials: X
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D000077144:Clopidogrel; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D019308:Palmitic Acid / Q000633:toxicity; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D019308:Palmitic Acid; D000077144:Clopidogrel; D013988:Ticlopidine