Wang Yihui, Chen Biyi, Huang Chun-Kai, Guo Ang, Wu Jennifer, Zhang Xiaoming, Chen Rong, Chen Cheng, Kutschke William, Weiss Robert M, Boudreau Ryan L, Margulies Kenneth B, Hong Jiang, Song Long-Sheng
Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
Division of Cardiovascular Medicine, Department of Internal Medicine & François M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine; Iowa City, Iowa.
JACC Basic Transl Sci. 2018 Aug 28;3(4):503-517. doi: 10.1016/j.jacbts.2018.05.004. eCollection 2018 Aug.
Heart failure remains a major cause of morbidity and mortality in developed countries. There is still a strong need to devise new mechanism-based treatments for heart failure. Numerous studies have suggested the importance of the Ca-dependent protease calpain in cardiac physiology and pathology. However, no drugs are currently under development or testing in human patients to target calpain for heart failure treatment. Herein the data demonstrate that inhibition of calpain activity protects against deleterious ultrastructural remodeling and cardiac dysfunction in multiple rodent models of heart failure, providing compelling evidence that calpain inhibition is a promising therapeutic strategy for heart failure treatment.
在发达国家，心力衰竭仍然是发病和死亡的主要原因。仍然迫切需要设计基于新机制的心力衰竭治疗方法。大量研究表明，钙依赖性蛋白酶钙蛋白酶在心脏生理和病理过程中具有重要作用。然而，目前尚无针对钙蛋白酶用于心力衰竭治疗的药物正在人类患者中进行研发或试验。本文的数据表明，在多种心力衰竭啮齿动物模型中，抑制钙蛋白酶活性可防止有害的超微结构重塑和心脏功能障碍，这提供了令人信服的证据，即抑制钙蛋白酶是一种有前景的心力衰竭治疗策略。
