Oligosaccharide Blocks PAR1 (Proteinase-Activated Receptor 1)-PAR4-Mediated Platelet Activation by Binding to Thrombin Exosite II and Impairs Thrombosis
文献类型：期刊论文
| 作者 | Li,Sujuan; Wang,Weili; Lin,Lisha; Yang,Lian; Cai,Ying; Yang,Xingzhi; Zhang,Taocui; Xiao,Chuang ; Yan,Hui; Gao,Na
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| 刊名 | ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
 |
| 出版日期 | 2023 |
| 卷号 | 43期号:2页码:253-266 |
| 关键词 | oligosaccharide platelet activation receptor protease-activated thrombin thrombosis ANTIPLATELET THERAPIES ALLOSTERIC LINKAGE TISSUE FACTOR PROTEASE VORAPAXAR MECHANISM REVEALS SITE |
| ISSN号 | 1524-4636 |
| DOI | 10.1161/ATVBAHA.122.318085 |
| 英文摘要 | Background:Inappropriate activation and aggregation of platelets can lead to arterial thrombosis. Thrombin is the most potent platelet agonist that activates human platelets via two PARs (proteinase-activated receptors), PAR1 and PAR4. The aim is to study the activity and mechanism of an oligosaccharide HS-11 (the undecasaccharide, derived from sea cucumber Holothuria fuscopunctata) in inhibiting thrombin-mediated platelet activation and aggregation and to evaluate its antithrombotic activity. Methods:Platelet activation was analyzed by detecting CD62P/P-selectin expression using flow cytometry. The HS-11-thrombin interaction and the binding site were studied by biolayer interferometry. Intracellular Ca2+ mobilization of platelets was measured by FLIPR Tetra System using Fluo-4 AM (Fluo-4 acetoxymethyl). Platelet aggregation, thrombus formation, and bleeding Assay were assessed. Results:An oligosaccharide HS-11, depolymerized from fucosylated glycosaminoglycan from sea cucumber Holothuria fuscopunctata blocks the interaction of thrombin with PAR1 and PAR4 complex by directly binding to thrombin exosite II, and completely inhibits platelet signal transduction, including intracellular Ca2+ mobilization and protein phosphorylation. Furthermore, HS-11 potently inhibits thrombin-PARs-mediated platelet aggregation and reduces thrombus formation in a model of ex vivo thrombosis. Conclusions:The study firstly report that the fucosylated glycosaminoglycan oligosaccharide has antiplatelet activity by binding to thrombin exosite II, and demonstrates that thrombin exosite II plays an important role in the simultaneous activation of PAR1 and PAR4, which may be a potential antithrombotic target for effective treatment of arterial thrombosis. |
| 学科主题 | Hematology ; Cardiovascular System & Cardiology |
| WOS记录号 | WOS:000920978000013 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/74916]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Li,Sujuan,Wang,Weili,Lin,Lisha,et al. Oligosaccharide Blocks PAR1 (Proteinase-Activated Receptor 1)-PAR4-Mediated Platelet Activation by Binding to Thrombin Exosite II and Impairs Thrombosis[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2023,43(2):253-266. |
| APA | Li,Sujuan.,Wang,Weili.,Lin,Lisha.,Yang,Lian.,Cai,Ying.,...&Zhao,Jinhua.(2023).Oligosaccharide Blocks PAR1 (Proteinase-Activated Receptor 1)-PAR4-Mediated Platelet Activation by Binding to Thrombin Exosite II and Impairs Thrombosis.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,43(2),253-266. |
| MLA | Li,Sujuan,et al."Oligosaccharide Blocks PAR1 (Proteinase-Activated Receptor 1)-PAR4-Mediated Platelet Activation by Binding to Thrombin Exosite II and Impairs Thrombosis".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 43.2(2023):253-266. |
入库方式： OAI收割
来源：昆明植物研究所
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