Department of Cardiothoracic Surgery, New York University School of Medicine, 530 First Avenue, New York, NY 10016, USA.
J Inflamm (Lond). 2010 Aug 30;7:45. doi: 10.1186/1476-9255-7-45.
Serine proteases are a key component of the inflammatory response as they are discharged from activated leukocytes and mast cells or generated through the coagulation cascade. Their enzymatic activity plays a major role in the body's defense mechanisms but it has also an impact on vascular homeostasis and tissue remodeling. Here we focus on the biological role of serine proteases in the context of cardiovascular disease and their mechanism(s) of action in determining specific vascular and tissue phenotypes. Protease-activated receptors (PARs) mediate serine protease effects; however, these proteases also exert a number of biological activities independent of PARs as they target specific protein substrates implicated in vascular remodeling and the development of cardiovascular disease thus controlling their activities. In this review both PAR-dependent and -independent mechanisms of action of serine proteases are discussed for their relevance to vascular homeostasis and structural/functional alterations of the cardiovascular system. The elucidation of these mechanisms will lead to a better understanding of the molecular forces that control vascular and tissue homeostasis and to effective preventative and therapeutic approaches.
丝氨酸蛋白酶是炎症反应的关键组成部分，因为它们从活化的白细胞和肥大细胞中释放出来，或者通过凝血级联反应产生。它们的酶活性在身体的防御机制中起着重要作用，但也对血管稳态和组织重塑有影响。在这里，我们关注丝氨酸蛋白酶在心血管疾病中的生物学作用及其在确定特定血管和组织表型中的作用机制。蛋白酶激活受体 (PARs) 介导丝氨酸蛋白酶的作用；然而，这些蛋白酶也通过靶向特定的蛋白质底物发挥许多独立于 PARs 的生物学活性，这些蛋白质底物参与血管重塑和心血管疾病的发展，从而控制它们的活性。在这篇综述中，讨论了丝氨酸蛋白酶的 PAR 依赖和非依赖作用机制，因为它们与血管稳态和心血管系统的结构/功能改变有关。阐明这些机制将有助于更好地理解控制血管和组织稳态的分子力，并为有效的预防和治疗方法提供依据。
