The RhoA/Rho kinase pathway in the myocardium.

The small GTPase RhoA and its downstream target Rho kinase (Rho-associated coiled-coil protein kinase or ROCK) are involved in cell contraction and a variety of other cellular processes via modulation of actin cytoskeletal assembly. Several studies, including investigations in humans, have clearly shown an important pathophysiological role of this pathway in the cardiovascular system and in disease states such as hypertension, heart failure, stroke, and diabetes [1]. The RhoA/ROCKpathway is best described in smoothmuscle cells, where it mediates calcium sensitization and thereby enhances and sustains contraction. However, the role of the RhoA/ROCK pathway in the myocardium is less well understood. Most studies on RhoA/ROCK in the heart address its involvement in cardiac hypertrophy and remodelling, and chronic inhibition of the pathway may prevent these long-term effects. In the current issue of Cardiovascular Research Lin et al. [2] describe a possible role of the RhoA/ROCK pathway in the contractile function of diabetic rat heart. These authors report that the decreased contractile function of hearts of diabetic animals was associated with an increased expression and activity of RhoA and ROCK. Interestingly, acute inhibition of ROCK improved cardiac performance in vivo and in vitro. These findings show an involvement of the RhoA/ ROCK pathway in diabetic cardiomyopathy and that this system is also involved in myocardial contraction.