Recent advances in the role of RhoA signaling in the heart.

Ras homolog family member A (RhoA) was originally discovered as a key regulator of cell cytoskeleton dynamics. Since then RhoA signaling research has expanded and it is now recognized that RhoA functions as a signaling hub that regulates diverse cellular functions, including cell growth, proliferation, and survival, both transcriptionally and post-transcriptionally. RhoA is activated in response to various stimuli such as G-protein coupled receptors (GPCRs), stretch and oxidative stress, and engages multiple downstream effectors. Rho-associated coiled-coil containing protein kinase (ROCK) is the first discovered effector of RhoA and other effectors include mammalian homolog of Diaphanous (mDia), phospholipase-Cε (PLCε), myocardin related transcription factor A (MRTF-A) and Yes-associated Protein (YAP). The role of RhoA in the heart has been extensively studied in last decades. Initially, studies using ROCK inhibitors suggested that activation of RhoA-ROCK signaling is deleterious in the heart, but recent studies have unveiled that RhoA in cardiomyocytes enhances fibrosis but confers cardioprotection against ischemic and non-ischemic stress through various mechanisms, including regulation of mitochondrial quality control. This review summarizes the recent progress of research on the role of RhoA signaling in the heart.