Plasminogen Activator Inhibitor 1 and Atherothrombosis
Plasminogen Activator Inhibitor 1 and Atherothrombosis
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纤溶酶原激活剂抑制剂 1 和动脉粥样硬化血栓形成
作者：
I. Juhan;M. Alessi
冠心病的临床表现主要是由于动脉粥样硬化斑块的进展和随后的血栓形成。纤维蛋白沉积在急性血栓性冠状动脉闭塞导致心肌梗死中的作用已被明确确立(1)。纤维蛋白逐渐进入血管壁也可能在动脉粥样硬化病变的发展中发挥作用（2-6）。纤维蛋白是人类动脉粥样硬化斑块的一致成分（6-9），并可能通过刺激平滑肌细胞增殖（10）以及与低密度脂蛋白，特别是脂蛋白(a)结合和积累（11,12）来促进斑块的生长。低纤溶导致纤维蛋白沉积去除减少（13）将是动脉粥样硬化血栓形成的主要候选因素。伴有动脉粥样硬化血栓形成的血浆纤溶蛋白溶解能力降低归因于纤溶酶原激活物抑制剂1 （pai - 1）水平升高，pai - 1是t -PA和尿激酶的主要生理抑制剂。最近的实验研究表明血浆PAI-1水平的升高确实具有血栓形成前的作用。PAI-1的升高会降低内源性和外源性纤维蛋白溶解，并增加血栓的延伸（14-16），而用特定抗体猝灭PAI-1活性则会产生相反的效果（17）。过度表达人类PAI-1基因的转基因小鼠在其四肢发生血栓形成（18）。此外，人类PAI-1缺乏最近被报道为异常出血的原因（19）。临床研究提示PAI-1表达增高具有致病意义，血浆图中PAI-1表达增高被认为是冠心病的生物学危险因素；局部，在动脉粥样硬化病变，它可能有利于血栓形成的现象。本综述将评估动脉粥样硬化血栓形成中全身或局部PAI-1水平升高的因果作用的流行病学和实验证据。
Clinical manifestations of coronary heart disease result principally from the progressive development of atherosclerotic plaques and subsequent thrombus formation. The role of fibrin deposition in the acute thrombotic occlusion of coronary arteries that leads to myocardial infarction has been clearly established (1). Progressive incorporation of fibrin into the vessel wall could also play a role in the development of the atherosclerotic lesion (2-6). Fibrin is a consistent component of human atherosclerotic plaques (6-9) and may contribute to plaque growth by stimulation of smooth muscle cell proliferation (10) and by binding and accumulating with low density lipoprotein, especially lipoprotein (a) (11,12). Hypofibrinolysis leading to decreased removal of fibrin deposits (13) would be a prime candidate for a role in the development of atherothrombosis. Reduced plasma fibrinolytic capacity accompanying atherothrombosis has been attributed to increased levels of plasminogen activator inhibitor 1 (PAI-I ) , the primary physiological inhibitor of t -PA and urokinase . Recen t exper imenta l d a t a have shown tha t increased plasma PAI-1 levels do indeed have a prothrombotic effect. Increased PAI-1 decreases endogenous and exogenous fibrinolysis and increases the extension of thrombosis (14-16), whereas quenching of PAI-1 activity with a specific antibody induces an opposite effect (17). Transgenic mice with overexpression of the human PAI-1 gene develop thrombosis in their extremities (18). Moreover, human PAI-1 deficiency was recently reported as a cause of abnormal bleeding (19). Clinical studies suggest that increased PAI-1 expression is of pathogenic significance and when present in plasma map be considered as a biological risk factor for coronary heart disease; locally, in the atherosclerotic lesion, it could favor a thrombotic phenomenon. This review will evaluate the epidemiological and experimental evidence for a causal role of systemic or local increase in PAI-1 levels in atherothrombosis.
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DOI：
10.1016/s0021-9258(18)52266-3
发表时间：
1991-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
O. Etingin;D P Hajjar;K. Hajjar;P. Harpel;R L Nachman
通讯作者：
O. Etingin;D P Hajjar;K. Hajjar;P. Harpel;R L Nachman
DOI：
10.1073/pnas.79.17.5312
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHILDS, CB;PROPER, JA;MOSES, HL
通讯作者：
MOSES, HL
血栓形成诱导的 1 型纤溶酶原激活剂抑制剂的动脉壁表达增强。
DOI：
10.1161/01.atv.12.12.1507
发表时间：
1992
期刊：
Arteriosclerosis and thrombosis : a journal of vascular biology
影响因子：
--
作者：
Sawa,H;Fujii,S;Sobel,BE
通讯作者：
Sobel,BE
血小板释放的生长因子可能减弱纤溶作用及其药理学意义。
DOI：
10.1016/0002-9149(89)90016-7
发表时间：
1989
期刊：
The American journal of cardiology
影响因子：
--
作者：
Fujii,S;Lucore,CL;Hopkins,WE;Billadello,JJ;Sobel,BE
通讯作者：
Sobel,BE
纤维蛋白溶解因子的饮食调节。
影响因子：
5.3
作者：
Mehrabian,M;Peter,JB;Barnard,RJ;Lusis,AJ
通讯作者：
Lusis,AJ