Skip to main content
Fig. 6 | Journal of Biomedical Science

Fig. 6

From: RhoA: a dubious molecule in cardiac pathophysiology

Fig. 6

Effectors of RhoA in cardiomyocyte hypertrophic signaling. In cardiomyocytes RhoA activation leads to the activation of cardio-protective signaling, but also signaling associated with heart failure. ROCK is the best studied downstream effector of RhoA. RhoA/ROCK activates LIMK, which promotes F-actin formation and stabilization via inhibition of cofilin. Interaction of AMOT-bound YAP with F-actin leads to release and translocation of YAP into the nucleus, and subsequently to the expression of genes for cell survival and adaptive hypertrophy. In contrast, the RhoA-induced reduction of G-actin promotes the translocation of MRTF-A into the nucleus, promoting pathological signaling. RhoA/ROCK activates PTEN and PI3K which convert PIP3 to PIP2, thus promoting PLC activation. PLC in turn converts PIP2 to IP3 and DAG. IP3 can stimulate the release of Ca2+ into the cytoplasm, which increases cardiomyocyte contractility. Besides, the increased Ca2+-level activate Calmodulin/CaMKII and CnA, inducing pathological signaling. DAG activates PKC and subsequently the MAPKinases JNK, p38 and ERK/MEK, which in turn promote the translocation of MEF2, GATA-4, SRF and MRTF-A into the nucleus and subsequently the expression of genes leading to pathological hypertrophy with heart failure

Back to article page