RhoA/Rho-kinase pathway: much more than just a modulation of vascular tone. Evidence from studies in humans.

RhoA/Rho-kinase signaling and its relationship/balance with the nitric oxide level, angiotensin II and vasopressors for cardiovascular pathophysiology is of increasing importance, and its involvement goes far beyond blood pressure regulation. The deep involvement of this pathway in cardiovascular biology is now known to include a wide spectrum of conditions relating to the long-term complications of hypertension, and in general of cardiovascular pathophysiology, such as changes in cardiovascular structure (remodeling) and the induction of atherosclerosis, involvement in the pathophysiological relationships between inflammation and hypertension, and in those between hypertension, glucose metabolism and insulin resistance. Studies from our laboratory have made an important contribution to the understanding of the cellular and molecular mechanisms mediated by the RhoA/Rho-kinase pathway, which include all the aspects of cardiovascular pathophysiology in which this pathway plays a role. In addition, if it is considered that our contribution to the clarification of these mechanisms only comes from studies in humans, their impact on the scenario of the RhoA/Rho-kinase pathway's biology, essentially supported by studies 'in vitro' or in animal models, is immediate. This review examines all the aspects of RhoA/Rho-kinase signaling in the light of the available data, and gives an updated and useful overall picture of its involvement in cardiovascular pathophysiology.