The annexin A2 system and vascular homeostasis.
The annexin A2 system and vascular homeostasis.
复制标题
膜联蛋白A2系统和血管稳态。
DOI：
10.1016/j.vph.2011.03.003
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发表时间：
2011-03
影响因子：
4
通讯作者：
Hajjar, Katherine A.
中科院分区：
文献类型：
--
作者：
Flood, Elle C.;Hajjar, Katherine A.
最佳的纤维蛋白平衡需要在内皮细胞表面精确控制纤溶酶的产生，内皮细胞排列在血管壁上。作为纤溶酶原和组织纤溶酶原激活物（tPA）的共受体，膜联蛋白A2（A2）复合物促进血管纤维蛋白溶解，所述纤溶酶原和组织纤溶酶原激活物是纤溶酶产生的关键因子。细胞内A2复合物是两个A2单体和两个相关蛋白p11拷贝的异源四聚体。响应于内皮细胞活化，A2被src-激酶磷酸化，并以高度调节的方式易位到细胞表面。A2的过度表达见于急性早幼粒细胞白血病的早期出血期，而抗磷脂综合征或脑静脉血栓形成中的高滴度A2抗体与血栓形成相关。此外，在实验性高同型半胱氨酸血症中，同型半胱氨酸对A2的衍生导致血管内纤维蛋白积聚和血管生成障碍，其特征在于Anxa2 −/−小鼠的表型。外源性A2也可能为缺血性血栓性卒中提供一种新的治疗方法，因为A2与传统的基于tPA的溶栓治疗联合给药可改善动物模型的结局。在这里，我们讨论了A2系统在血管内稳态中的作用，调节其促纤溶活性的分子相互作用，以及其在血管疾病的发病机制和治疗中的潜在作用。
Optimal fibrin balance requires precisely controlled plasmin generation on the surface of endothelial cells, which line the blood vessel wall. As a co-receptor for plasminogen and tissue plasminogen activator (tPA), which are key factors in plasmin generation, the annexin A2 (A2) complex promotes vascular fibrinolysis. The intracellular A2 complex is a heterotetramer of two A2 monomers and two copies of the associated protein, p11. In response to endothelial cell activation, A2 is phosphorylated by src-kinase, and translocated to the cell surface in a highly regulated manner. Over- expression of A2 is seen in acute promyelocytic leukemia during the early hemorrhagic phase, while high titer antibodies to A2, as in antiphospholipid syndrome or cerebral venous thrombosis, are associated with thrombosis. In experimental hyperhomocysteinemia, moreover, derivatization of A2 by homocysteine leads to intravascular fibrin accumulation and dysangiogenesis, features that phenocopy the Anxa2−/− mouse. Exogenous A2 may also offer a novel therapeutic approach to ischemic thrombotic stroke, as administration of A2 in conjunction with conventional tPA-based thrombolytic therapy improved outcome in an animal model. Here, we discuss the role of the A2 system in vascular homeostasis, the molecular interactions that regulate its profibrinolytic activity, and its potential role in the pathogenesis and treatment of vascular disease.
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影响因子：
20.3
作者：
Das, Riku;Burke, Tim;Plow, Edward F.
通讯作者：
Plow, Edward F.
DOI：
10.1073/pnas.192432299
发表时间：
2002-10-01
影响因子：
11.1
作者：
Beaton, AR;Rodriguez, J;Roy, P
通讯作者：
Roy, P
影响因子：
4.8
作者：
Deora, AB;Kreitzer, G;Hajjar, KA
通讯作者：
Hajjar, KA
影响因子：
8.3
作者：
Ferro, JM;Canhao, P;Barinagarrementeria, F
通讯作者：
Barinagarrementeria, F
影响因子：
4.8
作者：
Donier, E;Rugiero, F;Wood, JN
通讯作者：
Wood, JN