Protease Activity in Vascular Disease.
Protease Activity in Vascular Disease.
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DOI：
10.1161/atvbaha.119.312413
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发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
Megan Slack;S. Gordon
中科院分区：
文献类型：
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作者：
Megan Slack;S. Gordon
蛋白酶活性与血管疾病的发病机制有关，包括动脉粥样硬化、血栓形成和动脉瘤。涉及代表不同蛋白水解家族的多种蛋白酶及其相应的抑制剂。这些蛋白酶通过一系列重叠的途径导致血管疾病，这些途径影响血管壁的总体炎症状态和结构完整性。通过激活PAR（蛋白酶激活受体），这些酶传播炎症信号，细胞因子产生和炎症细胞募集。此外，蛋白酶可以降解动脉粥样硬化中的细胞外基质（ECM）、弹性膜和纤维帽的组分。流行的范式是过度的蛋白水解活性是血管疾病的起始和进展的重要贡献者。最近治疗血管病变的方法试图调节蛋白酶活性，以减少炎症并保持血管壁的结构完整性。这篇重点文章将回顾细胞外蛋白酶活性在血管病理学中作用的基础证据（图），重点是最新的发现和治疗方法。随着蛋白酶活性在血栓形成中的作用的最近综述，与动脉粥样硬化和动脉瘤相关的进展将主要被强调。
Protease activity has been implicated in the pathogenesis of vascular diseases, including atherosclerosis, thrombosis, and aneurysm. A wide variety of proteases representing different proteolytic families and their corresponding inhibitors are involved. These proteases contribute to vascular disease through a series of overlapping pathways that affect overall inflammatory status and structural integrity of the vessel wall. By activating PARs (protease-activated receptors), these enzymes propagate inflammatory signaling, cytokine production, and inflammatory cell recruitment. Additionally, proteases can degrade components of the extracellular matrix (ECM), elastic lamina, and fibrous cap in atheroma. The prevailing paradigm is that excessive proteolytic activity is a significant contributor to the initiation and progression of vascular disease. Recent approaches to treatment of vascular pathologies have attempted to modulate protease activity in an effort to reduce inflammation and preserve structural integrity of the vessel wall. This Highlight article will review foundational evidence for the role of extracellular protease activity in vascular pathology (Figure) with a focus on the most recent discoveries and approaches to treatment. Advances related to atherosclerosis and aneurysm will be primarily emphasized as the role of protease activity in thrombosis has been recently reviewed.