摘要
凝血因子Ⅻ(FⅫ)是内源性凝血通路和接触系统的起始分子。大量研究表明,基因敲除FⅫ或者药理学阻断FⅫ(a)能够显著抑制血栓形成,且不增加出血风险。FⅫ(a)除了在血栓形成中发挥作用外,还通过激活激肽系统产生缓激肽而引起炎症。在动物模型中,抑制FⅫ/FⅫa可抑制血栓形成和炎症反应。因此,FⅫ有望成为一个有效安全的抗血栓和炎症治疗的新靶点。目前,已有多种针对FⅫ(a)的小分子抑制剂或者抗体的研究。本文重点就FⅫ结构与功能、FⅫ接触激活在心血管血栓和炎症中的作用和机制、靶向药物研究进展方面进行综述。
The factorⅫ(FⅫ)is the initial molecular of endogenous coagulation pathway and contact systems.In recent years,numerous studies have shown that gene knockout of FⅫor pharmacological blocking of FⅫ(a)can significantly inhibit thrombosis without increasing the risk of bleeding.In addition to its role in thrombosis,FⅫa contributes to inflammation through the activation of the inflammatory bradykinin-producing kallikrein-kinin system.Pharmacological inhibition of FⅫ/FⅫa interferes with thrombosis and inflammation in animal models.Thus,targeting the FⅫseems to be a promising and safe therapeutic anticoagulation treatment strategy,with additional anti-inflammatory effects.Currently,a variety of small molecular inhibitors or antibodies for FⅫare being studied.In this review,we focuses on the structure of FⅫ,the role of FⅫcontact activation in cardiovascular thrombotic and inflammatory,and the progress of targeted medicine research.
作者
杨国丽
李慧慧
王淼
YANG Guo-li;LI Hui-hui;WANG Miao(Zhejiang Normal University,Academy of Chemistry and Life Sciences,321000;Chinese Academy of Medical Sciences Peking Union Medical College Hospital,Fuwai Hospital State,Key Laboratory of Cardiovascular Disease,100037)
出处
《中国分子心脏病学杂志》
CAS
2019年第6期3176-3180,共5页
Molecular Cardiology of China
基金
中国医学科学北京协和医学院学科建设基金
中国医学科学院创新工程基金(2017-12M-1-008,2016-I2M-1-003/005)。
关键词
FⅫ
血栓形成
炎症
靶向药物
FactorⅫ
Thrombosis
Inflammation
Targeted medicine
