Adiponectin acts as an endogenous antithrombotic factor
Adiponectin acts as an endogenous antithrombotic factor
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DOI：
10.1161/01.atv.0000194076.84568.81
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发表时间：
2006-01-01
影响因子：
8.7
通讯作者：
Kanakura, Y
中科院分区：
文献类型：
--
作者：
Kato, H;Kashiwagi, H;Kanakura, Y
目的：肥胖是胰岛素抵抗和心血管疾病的常见危险因素。虽然低脂联素血症与肥胖相关的代谢和血管疾病有关，但脂联素在血栓形成中的作用仍不清楚。方法和结果：我们研究了正常饮食饲养的脂联素基因敲除(APN-KO)雄性小鼠(8-12周龄)血小板血栓的形成。野生型(WT)和APN-KO小鼠的血小板计数和凝血参数无显著差异。然而，He-Ne激光对APN-KO小鼠的颈动脉损伤有加速血栓形成的作用(总血栓体积：APN-KO组为13.36+/-4.25×10(7)任意单位，WT组为6.74+/-2.87×10(7)任意单位；n=10；P<；0.01)。腺病毒介导的脂联素补充减轻了增强的血栓形成。在体外，切变率为250 S(-1)的I型胶原上的血栓形成以及低浓度激动剂诱导的血小板聚集均可促进APN-KO小鼠的血小板聚集，而重组脂联素则抑制这种聚集。在WT小鼠中，腺病毒介导的脂联素过表达可进一步抑制血栓的形成。结论：脂联素缺乏导致血栓形成和血小板聚集增加。本研究揭示了脂联素作为内源性抗血栓因子的新作用。
Objective: Obesity is a common risk factor in insulin resistance and cardiovascular diseases. Although hypoadiponectinemia is associated with obesity-related metabolic and vascular diseases, the role of adiponectin in thrombosis remains elusive.Methods and Results: We investigated platelet thrombus formation in adiponectin knockout (APN-KO) male mice (8 to 12 weeks old) fed on a normal diet. There was no significant difference in platelet counts or coagulation parameters between wild-type (WT) and APN-KO mice. However, APN-KO mice showed an accelerated thrombus formation on carotid arterial injury with a He-Ne laser (total thrombus volume: 13.36 +/- 4.25 x 10(7) arbitrary units for APN-KO and 6.74 +/- 2.87 x 10(7) arbitrary units for WT; n = 10; P < 0.01). Adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In vitro thrombus formation on a type I collagen at a shear rate of 250 s(-1), as well as platelet aggregation induced by low concentrations of agonists, was enhanced in APN-KO mice, and recombinant adiponectin inhibited the enhanced platelet aggregation. In WT mice, adenovirus-mediated overexpression of adiponectin additionally attenuated thrombus formation.Conclusion: Adiponectin deficiency leads to enhanced thrombus formation and platelet aggregation. The present study reveals a new role of adiponectin as an endogenous antithrombotic factor.