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心脏中 mTOR 信号的复杂网络。

The complex network of mTOR signalling in the heart.

机构信息

Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy.

IRCCS Neuromed Pozzilli, Via Atinense, 18, 86077 Pozzilli Italy.

出版信息

Cardiovasc Res. 2022 Jan 29;118(2):424-439. doi: 10.1093/cvr/cvab033.

Abstract

The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.

摘要

雷帕霉素靶蛋白(mTOR)整合了几种参与调节合成代谢和分解代谢过程的细胞内和细胞外信号。mTOR 组装成两个大分子复合物,称为 mTORC1 和 mTORC2,它们具有不同的调节剂、底物和功能。对 mTOR 信号的获得和丧失功能的动物模型的研究表明,mTORC1/2 在心血管系统中产生适应性和失调性功能。mTORC1 和 mTORC2 对于驱动心脏发育和心脏对压力等应激的适应都是不可或缺的,例如压力超负荷。然而,心脏中持续和失调的 mTORC1 激活在应激期间是有害的,并导致心脏重构以及遗传和代谢性心肌病的发展和进展。在这篇综述中,我们讨论了 mTOR 在心血管系统中的最新作用,包括在基础条件下和在压力下,如压力超负荷、缺血和代谢应激。目前的数据表明,mTOR 调节可能代表治疗心脏疾病的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca58/8932297/926d0ece86a7/cvab033f4.jpg

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