Small guanine nucleotide-binding protein Rho and myocardial function

Authors: Jun REN, Cindy X FANG


RhoA and Rho-kinase (ROCK) participate in a wide variety of cell signal functions
such as cell growth, smooth and cardiac muscle contraction, cytoskeleton
rearrangement, cell migration and proliferation. In vascular smooth muscle cells,
RhoA and ROCK play an important role in Ca2+ sensitization and regulate vascular
smooth muscle tone. In the heart, RhoA and ROCK mediate hypertrophic
response leading to cardiac hypertrophy. Recent cellular and molecular biology
studies using ROCK inhibitors such as Y-27632 and fasudil have indicated a
pivotal role of the RhoA-ROCK cascade in many aspects of cardiovascular function
such as cardiac hypertrophy and ventricular remodeling following myocardial
infarction. Inhibition of the RhoA-ROCK signaling pathway may be a suitable
target for a number of cardiovascular diseases including hypertension, atherosclerosis,
diabetes and hypertrophic heart failure. This review focuses on the
current understanding of the RhoA-ROCK signal pathway in heart diseases and
discusses the use of ROCK inhibitors as therapeutic agents for heart diseases
ranging from hypertensive cardiomyopathy to heart failure.

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