UMR_S702, INSERM, Université Pierre et Marie Curie-Paris6, Paris, France.
Cardiovasc Res. 2012 Oct 1;96(1):38-45. doi: 10.1093/cvr/cvs099. Epub 2012 Mar 16.
Calpains are cytosolic calcium-activated cysteine proteases. Recently, they have been proposed to influence signal transduction processes leading to myocardial remodelling and heart failure. In this review, we will first describe some of these molecular mechanisms. Calpains may contribute to myocardial hypertrophy and inflammation, mainly through the activation of transcription factors such as NF-κB. They play an important role in the fibrosis process partly by activating transforming growth factor β. They are also implicated in cell death as they cause the breakdown of sarcolemma and sarcomeres. Nevertheless, a key to understanding the molecular basis of calpain-mediated myocardial remodelling likely lies in the identification of mechanisms involved in calpain secretion, since cytosolic and extracellular proteases would have different functions. Finally, we will provide an overview of the available evidence that calpains are indeed actively involved in the common causes of heart failure, including hypertension, diabetes, atherosclerosis, ischaemia-reperfusion, atrial fibrillation, congestive failure, and mechanical unloading.
钙蛋白酶是细胞溶质钙激活的半胱氨酸蛋白酶。最近，它们被提出影响导致心肌重构和心力衰竭的信号转导过程。在这篇综述中，我们将首先描述其中一些分子机制。钙蛋白酶可能通过激活转录因子如 NF-κB 来促进心肌肥大和炎症。它们在纤维化过程中起着重要作用，部分原因是激活转化生长因子 β。它们还与细胞死亡有关，因为它们导致肌膜和肌节的破裂。然而，理解钙蛋白酶介导的心肌重构的分子基础的关键可能在于鉴定钙蛋白酶分泌所涉及的机制，因为细胞溶质和细胞外蛋白酶可能具有不同的功能。最后，我们将概述现有的证据，表明钙蛋白酶确实积极参与心力衰竭的常见原因，包括高血压、糖尿病、动脉粥样硬化、缺血再灌注、心房颤动、充血性心力衰竭和机械卸载。
