Weiss-Sadan Tommy, Gotsman Israel, Blum Galia
The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Heart Institute, Hadassah University Hospital, Jerusalem, Israel.
FEBS J. 2017 May;284(10):1455-1472. doi: 10.1111/febs.14043. Epub 2017 Mar 9.
Atherosclerosis predisposes patients to cardiovascular diseases, such as myocardial infarction and stroke. Instigation of vascular injury is triggered by retention of lipids and inflammatory cells in the vascular endothelium. Whereas these vascular lesions develop in young adults and are mostly considered harmless, over time persistent inflammatory and remodeling processes will ultimately damage the arterial wall and cause a thrombotic event due to exposure of tissue factors into the lumen. Evidence from human tissues and preclinical animal models has clearly established the role of cathepsin cysteine proteases in the development and progression of vascular lesions. Hence, understanding the function of cathepsins in atherosclerosis is important for developing novel therapeutic strategies and advanced point of care diagnostics. In this review we will describe the roles of cysteine cathepsins in different cellular process that become dysfunctional in atherosclerosis, such as lipid metabolism, inflammation and apoptosis, and how they contribute to arterial remodeling and atherogenesis. Finally, we will explore new horizons in protease molecular imaging, which may potentially become a surrogate marker to identify future cardiovascular events.
动脉粥样硬化使患者易患心血管疾病，如心肌梗死和中风。血管损伤的引发是由脂质和炎症细胞在血管内皮中的潴留所致。虽然这些血管病变在年轻人中就会出现，且大多被认为无害，但随着时间的推移，持续的炎症和重塑过程最终会损害动脉壁，并由于组织因子暴露于管腔而导致血栓形成事件。来自人体组织和临床前动物模型的证据已经明确证实了半胱氨酸组织蛋白酶在血管病变发生和发展中的作用。因此，了解组织蛋白酶在动脉粥样硬化中的功能对于开发新的治疗策略和先进的即时诊断方法至关重要。在这篇综述中，我们将描述半胱氨酸组织蛋白酶在动脉粥样硬化中功能失调的不同细胞过程中的作用，如脂质代谢、炎症和细胞凋亡，以及它们如何促进动脉重塑和动脉粥样硬化的发生。最后，我们将探索蛋白酶分子成像的新领域，其有可能成为识别未来心血管事件的替代标志物。
