Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Hypertension. 2011 Dec;58(6):978-86. doi: 10.1161/HYPERTENSIONAHA.111.180935. Epub 2011 Oct 10.
Atherosclerosis-based vascular disease is an inflammatory disease characterized by extensive remodeling of the extracellular matrix architecture of the arterial wall. Although matrix metalloproteinases and serine proteases participate in these pathological events, the discovery of cysteine protease cathepsins, such as cathepsins K, S, L, and B, and cystatin C, and their tissue distribution has suggested that at least some of them participate in cardiovascular disease. Studies on vascular cells have shown that atherosclerosis-associated inflammatory cytokines augment cysteinyl cathepsin expression and activity. Novel insight into cathepsin functions has been made possible by the generation and in-depth analysis of knockout and transgenic mice. These studies have provided direct evidence implicating cathepsins in atherosclerosis-based vascular disease through the activation, liberation, and modification of angiogenic growth factors, cytokines, and proteases associated with lipid metabolism, cell events (migration, invasion, proliferation, and apoptosis), angiogenesis, and matrix protein remodeling. Furthermore, evaluation of the feasibility of cathepsins as a diagnostic tool has revealed that the serum cathepsins S and L and the endogenous inhibitor cystatin C hold promise as biomarkers of coronary artery disease and aneurysm formation. The goal of this review is to summarize the available information regarding the mechanistic contributions of cathepsins in atherosclerosis-based vascular disease.
基于动脉粥样硬化的血管疾病是一种炎症性疾病，其特征是动脉壁细胞外基质结构的广泛重塑。尽管基质金属蛋白酶和丝氨酸蛋白酶参与这些病理事件，但半胱氨酸蛋白酶组织蛋白酶如组织蛋白酶 K、S、L 和 B 以及半胱氨酸蛋白酶抑制剂 C 的发现表明，至少其中一些参与了心血管疾病。对血管细胞的研究表明，与动脉粥样硬化相关的炎症细胞因子会增加半胱氨酸蛋白酶的表达和活性。通过生成和深入分析基因敲除和转基因小鼠，对半胱天冬酶功能的新认识成为可能。这些研究通过激活、释放和修饰与脂质代谢、细胞事件（迁移、侵袭、增殖和凋亡）、血管生成和基质蛋白重塑相关的血管生成生长因子、细胞因子和蛋白酶，为半胱天冬酶在基于动脉粥样硬化的血管疾病中的作用提供了直接证据。此外，对半胱天冬酶作为诊断工具的可行性的评估表明，血清组织蛋白酶 S 和 L 以及内源性抑制剂半胱氨酸蛋白酶 C 有望成为冠心病和动脉瘤形成的生物标志物。本文综述的目的是总结关于半胱天冬酶在基于动脉粥样硬化的血管疾病中的作用机制的现有信息。
