Rho/Rho kinase signal transduction pathway in cardiovascular disease and cardiovascular remodeling. La vía de señalización Rho/Rho-cinasa en la enfermedad y el remodelado cardiovascular.

Abstract

The small guanosine triphosphatase Rho and its target, Rho kinase, play important roles in both blood pressure regulation and vascular smooth muscle contraction. Rho is activated by agonists of receptors coupled to cell membrane G protein, such as angiotensin II and phenylephrine. Once Rho is activated, it translocates to the cell membrane where it, in turn, activates Rho kinase. Activated Rho kinase phosphorylates myosin light chain phosphatase, which is then inhibited. This sequence stimulates vascular smooth muscle contraction, stress fiber formation, and cell migration. In this way, Rho and Rho kinase activation have important effects on several cardiovascular diseases. Currently available substances that specifically inhibit this signaling pathway could offer clinical benefits in several cardiovascular, as well as non-cardiovascular, diseases, such as arterial hypertension, pulmonary hypertension, cerebral or coronary spasm, post-angioplasty restenosis, and erectile dysfunction.