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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

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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.

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Acknowledgments

This study was funded by the Associated Project of Yunnan Province Science & Technology Department and Kunming Medical University Basic Research for Application (Code: 2013FB148).

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Authors and Affiliations

  1. Department of Rheumatology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, China

    Jing Wang

  2. Department of Orthopaedics, The First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming, 650032, Yunnan, China

    Lingqiang Chen, Hongfei Li, Jin Yang, Zhiqiang Gong, Bing Wang & Xueling Zhao

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  1. Jing Wang
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  2. Lingqiang Chen
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  3. Hongfei Li
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  7. Xueling Zhao
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Correspondence to Lingqiang Chen.

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Wang, J., Chen, L., Li, H. et al. 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. Mol Cell Biochem 404, 203–210 (2015). https://doi.org/10.1007/s11010-015-2379-1

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  • DOI: https://doi.org/10.1007/s11010-015-2379-1

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