CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
IMPACT OF IMPAIRED GLUCOSE TOLERANCE AND INSULIN RESISTANCE IN HEART INJURY: ROL OF Ca2+-CALMODULIN KINASE II (CaMKII).
LEANDRO SOMMESE; PAULA BLANCO; JO. VELEZ RUEDA; CECILIA CASTRO; CAROLINA ZANUZZI; ENRIQUE PORTIANSKY; ALICIA MATTIAZZI; JULIETA PALOMEQUE
Santiago de Chile
Congreso; XX Meeting ISHR Latin American Section; 2012
Although impaired glucose tolerance (IGT) and CaMKII are linked to cardiac disease, the nexus between IGT and CaMKII in the heart has never been explored. To reach this goal we used an IGT model induced by a fructose-rich diet (control, C; and fructose, F; rats or mice), and we performed echocardiography, biochemical studies, TBARS, and Ca2+i measurements. F rats showed decreased contractility and increased hypertrophy by echocardiography associated with increased CaMKII activity (P-CaMKII 100.2±24.2% and P-Thr17 of phospholamban 169.0±51.4%), P-p38MAPK (61.7±13.9%), ROS (106.7±28.5%) and apoptosis (increased Bax/Bcl2 [273.6±39.7%] and TUNEL positive cells) with respect to C rats. Myocytes from F rats showed decreased inotropic reserve to isoproterenol and increased non stimulated events, which were prevented by pretreatment of the myocytes with KN93, a CaMKII inhibitor. ROS increased either in F mice which express a CaMKII inhibitor (AC3I) or in the control strain (AC3C), however, C AC3I showed lower ROS than C AC3C, indicating that ROS production is both, dependent and independent of CaMKII activity. Altogether, the results would indicate a link between CaMKII activation and TGA.