The Ras homolog gene family member A (RhoA) is the founding member of Rho GTPase superfamily originally studied in cancer cells where it was found to stimulate cell cycle progression and migration. RhoA acts as a master switch control of actin dynamics essential for maintaining cytoarchitecture of a cell. In the last two decades, however, RhoA has been coined and increasingly investigated as an essential molecule involved in signal transduction and regulation of gene transcription thereby affecting physiological functions such as cell division, survival, proliferation and migration. RhoA has been shown to play an important role in cardiac remodeling and cardiomyopathies; underlying mechanisms are however still poorly understood since the results derived from in vitro and in vivo experiments are still inconclusive. Interestingly its role in the development of cardiomyopathies or heart failure remains largely unclear due to anomalies in the current data available that indicate both cardioprotective and deleterious effects. In this review, we aimed to outline the molecular mechanisms of RhoA activation, to give an overview of its regulators, and the probable mechanisms of signal transduction leading to RhoA activation and induction of downstream effector pathways and corresponding cellular responses in cardiac (patho)physiology. Furthermore, we discuss the existing studies assessing the presented results and shedding light on the often-ambiguous data. Overall, we provide an update of the molecular, physiological and pathological functions of RhoA in the heart and its potential in cardiac therapeutics.

中文翻译：

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RhoA：心脏病理生理学中的一个可疑分子

Ras 同源基因家族成员 A (RhoA) 是 Rho GTPase 超家族的创始成员，最初在癌细胞中进行研究，发现它可以刺激细胞周期进程和迁移。RhoA 充当维持细胞细胞结构必不可少的肌动蛋白动力学的主开关控制。然而，在过去的二十年中，RhoA 已被创造并越来越多地被研究为参与信号转导和基因转录调控的重要分子，从而影响细胞分裂、存活、增殖和迁移等生理功能。RhoA 已被证明在心脏重塑和心肌病中发挥重要作用。然而，由于来自体外和体内实验的结果仍然没有定论，因此对潜在的机制仍然知之甚少。有趣的是，它在心肌病或心力衰竭发展中的作用在很大程度上仍不清楚，因为当前可用数据中的异常表明心脏保护作用和有害作用。在这篇综述中，我们旨在概述 RhoA 激活的分子机制，概述其调节因子，以及导致 RhoA 激活和诱导下游效应通路的信号转导的可能机制以及心脏（病理）生理学中的相应细胞反应. 此外，我们讨论了评估所呈现结果的现有研究，并阐明了经常模棱两可的数据。总体而言，我们提供了 RhoA 在心脏中的分子、生理和病理功能及其在心脏治疗中的潜力的更新。