Abstract 16134: Different Roles of Myocardial ROCK1 and ROCK2 in Response to Chronic Pressure-Overload in Mice

Background: Rho-kinase plays a crucial role in the development of cardiac hypertrophy and failure. However, possible different roles of myocardial Rho-kinase isoforms, ROCK1 and ROCK2, remain to be elucidated. Methods and Results: We performed transverse aortic constriction (TAC) in cardiac-specific ROCK1-deficient (ROCK1-/-) mice, cardiac-specific ROCK2-deficient (ROCK2-/-) mice, and their littermate controls, and thereafter examined the time-course for 4 weeks. Echocardiography revealed that ROCK1-/- mice were vulnerable to pressure-overload associated with LV dilatation and reduced contractility. In contrast, ROCK2-/- mice showed less LV hypertrophy and preserved LV diastolic function compared with controls after TAC. Histological analysis showed that pressure-overload-induced cardiac hypertrophy and fibrosis were enhanced in ROCK1-/- mice compared with controls, whereas cardiac hypertrophy was attenuated in ROCK2-/- mice after TAC. Consistently, as compared with respective controls, ROCK1-/- mice show...