Department of Cardiology, Peking University Third Hospital, Beijing, P.R. China.
Department of Critical Care Medicine, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, P.R. China.
J Cell Mol Med. 2024 Sep;28(17):e70064. doi: 10.1111/jcmm.70064.
Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within the acidic milieu of lysosomes to facilitate recycling. Recent research has revealed that CTSB plays a multifaceted role beyond its function as a proteolytic enzyme in lysosomes. Importantly, recent data suggest that CTSB has significant impacts on different cardiac pathological conditions, such as atherosclerosis (AS), myocardial infarction, hypertension, heart failure and cardiomyopathy. Especially in the context of AS, preclinical models and clinical sample imaging data indicate that the cathepsin activity-based probe can reliably image CTSB activity in foam cells and atherosclerotic plaques; concurrently, it allows synchronous diagnostic and therapeutic interventions. However, our knowledge of CTSB in cardiovascular disease is still in the early stage. This paper aims to provide a comprehensive review of the significance of CTSB in cardiovascular physiology and pathology, with the objective of laying a theoretical groundwork for the development of drugs targeting CTSB.
组织蛋白酶 B(CTSB)是半胱氨酸蛋白酶家族的一员,主要负责降解溶酶体酸性环境中不必要的细胞器和蛋白质,以促进回收。最近的研究表明,CTSB 在溶酶体中作为蛋白水解酶的功能之外,还具有多方面的作用。重要的是,最近的数据表明,CTSB 对不同的心脏病理状况有重大影响,如动脉粥样硬化(AS)、心肌梗死、高血压、心力衰竭和心肌病。特别是在 AS 的背景下,临床前模型和临床样本成像数据表明,基于组织蛋白酶活性的探针可以可靠地对泡沫细胞和动脉粥样硬化斑块中的 CTSB 活性进行成像;同时,它允许进行同步的诊断和治疗干预。然而,我们对心血管疾病中 CTSB 的认识仍处于早期阶段。本文旨在全面综述 CTSB 在心血管生理学和病理学中的意义,为靶向 CTSB 的药物开发奠定理论基础。