title: Homocysteine enhances clot-promoting activity of endothelial cells via phosphatidylserine externalization and microparticles formation.
abstract: Total elevated plasma homocysteine (Hcy) is a risk factor for thromboembolism. Vascular endothelium is important to regulate coagulation, but the impact of Hcy on the clot-promoting activity (CPA) of endothelial cells has not been fully understood. In our study, human umbilical vein endothelial cells (HUVECs) were treated with Hcy (8, 20, 80, 200, 800 μmol/L) for 24 h. Annexin V was utilized to detect phosphatidylserine (PS) externalization and endothelial microparticles (MPs) formation. CPA was assessed by recalcification time and purified clotting complex tests. We found that Hcy enhanced the externalized PS and consequent CPA of HUVECs in a dose-dependent fashion, effect of Hcy had statistical significance at 800 μmol/L. In addition, Hcy also increased the shedding of procoagulant endothelial MPs. Blocking of PS with 128 nmol/L annexin V reduced approximately 70% CPA of HUVECs and endothelial MPs, but human anti-tissue factor antibody had little inhibitive effect. Our results showed that Hcy increased CPA of HUVECs via PS externalization and MPs release. Our present study has implications for hyperhomocysteinemia-related hypercoagulability.
authors.affiliation: Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China.
authors.forename: Jiuxin
authors.initials: J
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.forename: Xianmei
authors.initials: X
authors.lastname: Piao
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Hou
authors.forename: Chongbao
authors.initials: C
authors.lastname: Zhao
authors.forename: Guofen
authors.initials: G
authors.lastname: Qiao
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D003029:Coagulants / Q000494:pharmacology*; D006710:Homocysteine / Q000494:pharmacology* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism*; D013918:Thrombin Time
chemical_list: D003029:Coagulants; D010718:Phosphatidylserines; D006710:Homocysteine