Laboratory of Cardiovascular Diseases, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Cardiology, West China Hospital, Sichuan University, Chengdu 610041, China.
Oxid Med Cell Longev. 2022 Apr 11;2022:2531458. doi: 10.1155/2022/2531458. eCollection 2022.
Diabetic cardiomyopathy (DCM), as a serious complication of diabetes, causes structural and functional abnormalities of the heart and eventually progresses to heart failure. Currently, there is no specific treatment for DCM. Studies have proved that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are key factors for the development and progression of DCM. The mitochondria-associated ER membranes (MAMs) are a unique domain formed by physical contacts between mitochondria and ER and mediate organelle communication. Under high glucose conditions, changes in the distance and composition of MAMs lead to abnormal intracellular signal transduction, which will affect the physiological function of MAMs, such as alter the Ca homeostasis in cardiomyocytes, and lead to mitochondrial dysfunction and abnormal apoptosis. Therefore, the dysfunction of MAMs is closely related to the pathogenesis of DCM. In this review, we summarized the evidence for the role of MAMs in DCM and described that MAMs participated directly or indirectly in the regulation of the pathophysiological process of DCM via the regulation of Ca signaling, mitochondrial dynamics, ER stress, autophagy, and inflammation. Finally, we discussed the clinical transformation prospects and technical limitations of MAMs-associated proteins (such as MFN2, FUNDC1, and GSK3) as potential therapeutic targets for DCM.
糖尿病心肌病（DCM）作为糖尿病的严重并发症，导致心脏结构和功能异常，最终进展为心力衰竭。目前，DCM 没有特定的治疗方法。研究已经证明，线粒体功能障碍和内质网（ER）应激是 DCM 发生和发展的关键因素。线粒体相关内质网膜（MAMs）是由线粒体和 ER 之间的物理接触形成的独特结构域，介导细胞器间的通讯。在高葡萄糖条件下，MAMs 的距离和组成的变化导致细胞内信号转导异常，从而影响 MAMs 的生理功能，例如改变心肌细胞中的 Ca 稳态，导致线粒体功能障碍和异常凋亡。因此，MAMs 的功能障碍与 DCM 的发病机制密切相关。在这篇综述中，我们总结了 MAMs 在 DCM 中的作用证据，并描述了 MAMs 通过调节 Ca 信号、线粒体动力学、ER 应激、自噬和炎症，直接或间接地参与 DCM 病理生理过程的调节。最后，我们讨论了 MAMs 相关蛋白（如 MFN2、FUNDC1 和 GSK3）作为 DCM 潜在治疗靶点的临床转化前景和技术局限性。
