Rho/Rho-kinase and C-reactive protein relationship in hypertension and atherosclerosis

1Department of Clinical and Experimental Medicine Clinica Medica 42 Laboratory Medicine University of Padova Italy3 Department of Nutrition University of California Davis USA Sir, RhoA/Rho kinase pathway has been advanced in the pathogenesis of hypertension and atherosclerosis [1]. This is based on its modulation of regulatory chain phosphorylation of myosin II which contributes to smooth muscle Ca2+ sensitization [2], increased expression of NAD(P)H oxidase [3] and induction of oxidative stress. In addition, Rho kinase activation regulates endothelial nitric oxide synthase [4] and also controls the production of the profibrotic plasminogen activator inhibitor-1 (PAI-1) [5] and inhibition of Rho kinase results in the suppression of neointimal formation [6], activation of Akt pathway and eNOS [7], further confirming an important role of Rho/Rho kinase inhibition for cardiovascular protection and prevention of atherogenesis. Evidence has been recently provided for the involvement of Rho/Rho-kinase signaling in C Reactive Protein (CRP)-induced atherothrombogenesis. CRP has been shown, in fact, to activate Rho/Rho-kinase signaling, which through activation of NFκB activity results in PAI-1 expression, known atherothrombogenic factor. This suggests Rho/Rho-kinase inhibition as a potential therapeutic strategy for the prevention of atherogenesis [8].