Background: Cardiac hypertrophy is an adaptive response to increased load, triggered to maintain cardiac output. However, prolonged cardiac hypertrophy is a risk factor for arrhythmias, heart failure and sudden death. Recently, Kehat et al. showed that activation or silencing of the reperfusion injury salvage kinase (RISK) biochemical pathway affects the development of hypertrophy in mice. In this study, our aim was to examine changes in the RISK pathway proteins expression in various models of cardiac remodeling. Methods: We established clinical scenarios of cardiac remodeling in rats, including: hypertension, aortic stenosis and anemia, all of which cause cardiac eccentric or concentric hypertrophy. Hypertrophy was determined using echocardiographic measurements and histological analysis. The expression of the RISK pathway proteins: ERK1/2, p-ERK1/2 and p-MEK1/2 was analyzed using Western blot. Results: Anemic rats characterized by decreased hemoglobin level (12±1 gr./dl vs. 15±1 gr./dl, respectively P<0.001), lowered iron blood concentration (68.1±22.6 µg/dl vs. 182.8±70.7 µg/dl, respectively, P<0.001) and decreased mean capsular volume (65.8±17.1 fl vs. 93.5±20.8 fl, respectively, p<0.05). Anemia induced an eccentric hypertrophy: anemic rats left ventricle (LV) cavity area increased significantly (7.5±3.2 mm2 vs. 4.8±1.9 mm2, anemia and control, respectively, P<0.05). Concomitantly, ERK1/2 and p-ERK1/2 expressions were decreased while p-MEK1/2 expression increased in the anemic group. In a model of hypertension concentric hypertrophy was induced: LV cavity area increased (5.5±1.4 mm2 vs. 3.9±1.7 mm2 in hypertension and control, respectively, P=0.07). Hypertensive rats had lower body weight (361.2±23.4 gr. vs. 400.3±20.86 gr., P<0.01); however, their heart to body weight ratio was increased (3.79±0.53 vs. 3.17±0.23, P<0.001). ERK1/2 and p-ERK1/2 expressions were increased while p-MEK1/2 expression decreased. Conclusions: The expression of ERK1/2, p-ERK1/2 and p-MEK1/2 correlates with the type of hypertrophic development (concentric or eccentric).
