Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions.
Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions.
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DOI：
10.1111/j.1755-5922.2010.00171.x
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发表时间：
2010-10
影响因子：
3.1
通讯作者：
Incalzi RA
中科院分区：
文献类型：
--
作者：
Cesari M;Pahor M;Incalzi RA
在过去的十年里，人们越来越多地研究衰老和血栓形成之间的密切关系。在心脑血管风险增加的基础上，已经假设与年龄相关的血栓形成前纤溶平衡失衡的发展。纤溶作用是多种纤溶酶原激活剂和抑制物相互作用的结果，构成了酶促反应级联反应，最终导致纤维蛋白的降解。纤溶酶原激活系统在广泛的生理和病理过程中起着关键作用。纤溶酶原激活物抑制物-1(PAI-1)是丝氨酸蛋白酶抑制物(或蛇毒)超家族成员之一，是组织型和尿型纤溶酶原激活物的主要抑制物，这两种纤溶酶原激活剂均可激活纤溶酶原。在这篇综述中，目前的证据描述了PAI-1在许多与年龄相关的亚临床(如炎症、动脉粥样硬化、胰岛素抵抗)和临床(如肥胖、合并症、Werner综合征)中所起的核心作用。尽管存在一些争议和不清楚的问题，PAI-1仍是一个极具前景的标志物，它可能成为一个生物学参数，在预后评估、疾病监测和未来年龄相关疾病的治疗靶点中被越来越多地考虑。
The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a pro-thrombotic imbalance in the fibrinolysis homeostasis has been hypothesized at the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the resulting of the interactions among multiple plasminogen activators and inhibitors constituing the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen. In this review, current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker which may become a biological parameter to be growingly considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the next future.
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