Rho-associated kinase activity, endothelial function, and cardiovascular risk factors.

OBJECTIVE Cardiovascular diseases are associated with chronic activation of Rho-associated kinases (ROCKs) and endothelial dysfunction. Both increased ROCK activity and endothelial dysfunction are thought to be closely associated with conventional cardiovascular risk factors. The purpose of this study was to determine the relationships between ROCK activity, endothelial function, and cardiovascular risk factors. METHODS AND RESULTS We evaluated ROCK activity in peripheral leukocytes by Western blot analysis and flow-mediated vasodilation by ultrasonography in 242 men who had no cardiovascular or cerebrovascular diseases (mean age, 40±10 years; range, 20 to 73 years). ROCK activity was defined as the ratio of phospho myosin-binding subunit on myosin light chain phosphatase to total myosin-binding subunit. Univariate regression analysis revealed that leukocyte ROCK activity significantly correlated with body mass index (r=0.29, P=0.003); systolic blood pressure (r=0.25, P=0.01); low-density lipoprotein cholesterol level (r=0.21, P=0.04); and Framingham risk factor score, a cumulative cardiovascular risk index for heart attack (r=0.31, P<0.001), and that flow-mediated vasodilation significantly correlated with age (r=-0.23, P=0.02), body mass index (r=0.19, P=0.05), systolic blood pressure (r=-0.22, P=0.03), total cholesterol level (r=-0.21, P=0.04), low-density lipoprotein cholesterol level (r=-0.22, P=0.04), glucose level (r=-0.20, P=0.04), and Framingham risk factor score (r=-0.37, P<0.001). There was a significant correlation between leukocyte ROCK activity and flow-mediated vasodilation (r=-0.41, P<0.001). Multivariate analysis revealed that flow-mediated vasodilation was an independent predictor of leukocyte ROCK activity. CONCLUSIONS These findings suggest that cumulative cardiovascular risk may enhance ROCK activity and endothelial dysfunction, leading to progression of cardiovascular diseases and outcomes.