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OxLDL enhances procoagulant activity of endothelial cells by TMEM16F-mediated phosphatidylserine exposure.
Yan, Meishan; Wang, Zelong; An, Yao; Li, Zhanni; Li, Yun; Zhang, Hongyu; Li, Caixia; Wang, Lifeng; Chen, Li; Gao, Chao; Wang, Dongsheng; Gao, Chunyan.
Afiliação
  • Yan M; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Wang Z; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • An Y; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Li Z; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Li Y; Hematology Department, Daqing Oil Field General Hospital, Daqing, China.
  • Zhang H; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Li C; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Wang L; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Chen L; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Gao C; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
  • Wang D; Department of Emergency, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China.
  • Gao C; Department of Medical Laboratory Science and Technology, Harbin Medical University Daqing, Daqing, China.
Cell Biol Int ; 48(6): 848-860, 2024 Jun.
Article em En | MEDLINE | ID: mdl-38444077
ABSTRACT
Oxidized low-density lipoprotein (oxLDL), a key component in atherosclerosis and hyperlipidemia, is a risk factor for atherothrombosis in dyslipidemia, yet its mechanism is poorly understood. In this study, we used oxLDL-induced human aortic endothelial cells (HAECs) and high-fat diet (HFD)-fed mice as a hyperlipidemia model. Phosphatidylserine (PS) exposure, cytosolic Ca2+, reactive oxygen species (ROS), and lipid peroxidation were measured by flow cytometer. TMEM16F expression was detected by immunofluorescence, western blot, and reverse transcription polymerase chain reaction. Procoagulant activity (PCA) was measured by coagulation time, intrinsic/extrinsic factor Xase, and thrombin generation. We found that oxLDL-induced PS exposure and the corresponding PCA of HAECs were increased significantly compared with control, which could be inhibited over 90% by lactadherin. Importantly, TMEM16F expression in oxLDL-induced HAECs was upregulated by enhanced intracellular Ca2+ concentration, ROS, and lipid peroxidation, which led to PS exposure. Meanwhile, the knockdown of TMEM16F by short hairpin RNA significantly inhibited PS exposure in oxLDL-induced HAECs. Moreover, we observed that HFD-fed mice dramatically increased the progress of thrombus formation and accompanied upregulated TMEM16F expression by thromboelastography analysis, FeCl3-induced carotid artery thrombosis model, and western blot. Collectively, these results demonstrate that TMEM16F-mediated PS exposure may contribute to prothrombotic status under hyperlipidemic conditions, which may serve as a novel therapeutic target for the prevention of thrombosis in hyperlipidemia.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatidilserinas / Espécies Reativas de Oxigênio / Células Endoteliais / Anoctaminas / Lipoproteínas LDL Limite: Animals / Humans Idioma: En Revista: Cell Biol Int Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatidilserinas / Espécies Reativas de Oxigênio / Células Endoteliais / Anoctaminas / Lipoproteínas LDL Limite: Animals / Humans Idioma: En Revista: Cell Biol Int Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China