Sjöberg Sara, Shi Guo-Ping
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Clin Rev Bone Miner Metab. 2011 Jun 1;9(2):138-147. doi: 10.1007/s12018-011-9098-2. Epub 2011 Jun 18.
Extracellular matrix remodeling is an important mechanism in the initiation and progression of cardiovascular diseases. Cysteine protease cathepsins are among the important proteases that affect major events in the pathogenesis of atherosclerosis and abdominal aortic aneurysm, including smooth muscle cell transmigration through elastic lamina, macrophage foam cell formation, vascular cell and macrophage apoptosis, and plaque rupture. These events have been studied in cathepsin deficiencies and cathepsin inhibitor deficiencies in mice and have provided invaluable insights regarding the roles of cathepsins in cardiovascular diseases. Pharmacological inhibitions for cathepsins are under evaluation for other human diseases and may be used as clinical treatments for cardiovascular diseases in the near future. This article reviews different mechanisms for cathepsins in atherosclerosis and abdominal aortic aneurysm that could be targeted by selective cathepsin inhibitors.
细胞外基质重塑是心血管疾病发生和发展的重要机制。半胱氨酸蛋白酶组织蛋白酶是影响动脉粥样硬化和腹主动脉瘤发病机制中主要事件的重要蛋白酶之一，这些事件包括平滑肌细胞穿过弹性膜迁移、巨噬细胞泡沫细胞形成、血管细胞和巨噬细胞凋亡以及斑块破裂。在小鼠的组织蛋白酶缺陷和组织蛋白酶抑制剂缺陷中对这些事件进行了研究，这些研究为组织蛋白酶在心血管疾病中的作用提供了宝贵的见解。组织蛋白酶的药理学抑制作用正在针对其他人类疾病进行评估，并且在不久的将来可能用作心血管疾病的临床治疗方法。本文综述了组织蛋白酶在动脉粥样硬化和腹主动脉瘤中的不同作用机制，这些机制可能成为选择性组织蛋白酶抑制剂的作用靶点。
