Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease.
Alpha2-Antiplasmin: The Devil You Don't Know in Cerebrovascular and Cardiovascular Disease.
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DOI：
10.3389/fcvm.2020.608899
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发表时间：
2020
影响因子：
3.6
通讯作者：
Reed GL
中科院分区：
文献类型：
--
作者：
Singh S;Saleem S;Reed GL
α 2-抗纤溶酶（α2AP）是纤溶酶的快速反应丝氨酸蛋白酶抑制剂（serpin），最初被认为在对抗纤溶酶介导的凝血因子和其他分子的不受控制的蛋白水解中起关键作用。然而，对α2AP遗传缺陷的人类和小鼠的研究扩大了我们对这种丝氨酸蛋白酶抑制剂的理解，特别是在疾病状态下。流行病学研究表明，高α2AP水平与心血管疾病风险增加或预后不良之间存在关联。在疾病模型中的机制研究表明，α2AP阻止身体自身的纤溶系统溶解导致静脉血栓形成、肺栓塞、动脉血栓形成和缺血性卒中的病理性血栓。此外，α2AP促进微血管血栓形成的发展并增强基质金属蛋白酶-9的表达。通过这些机制和其他机制，α2AP有助于实验性缺血性卒中中的脑损伤、出血和肿胀。最近的研究还表明，α2AP通过抑制有效纤溶的早期激活而在血栓形成中起重要作用。本文就α2AP在控制血栓形成和纤溶中的作用及其作为心血管疾病和缺血性脑卒中治疗靶点的潜在价值作一综述。
Alpha2-antiplasmin (α2AP), the fast-reacting, serine protease inhibitor (serpin) of plasmin, was originally thought to play a key role in protection against uncontrolled, plasmin-mediated proteolysis of coagulation factors and other molecules. However, studies of humans and mice with genetic deficiency of α2AP have expanded our understanding of this serpin, particularly in disease states. Epidemiology studies have shown an association between high α2AP levels and increased risk or poor outcome in cardiovascular diseases. Mechanistic studies in disease models indicate that α2AP stops the body's own fibrinolytic system from dissolving pathologic thrombi that cause venous thrombosis, pulmonary embolism, arterial thrombosis, and ischemic stroke. In addition, α2AP fosters the development of microvascular thrombosis and enhances matrix metalloproteinase-9 expression. Through these mechanisms and others, α2AP contributes to brain injury, hemorrhage and swelling in experimental ischemic stroke. Recent studies also show that α2AP is required for the development of stasis thrombosis by inhibiting the early activation of effective fibrinolysis. In this review, we will discuss the key role played by α2AP in controlling thrombosis and fibrinolysis and, we will consider its potential value as a therapeutic target in cardiovascular diseases and ischemic stroke.
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发表时间：
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影响因子：
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