CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
ENDOGENOUS ANGIOTENSIN II- INDUCED CARDIAC APOPTOSIS IN VIVO IS MEDIATED BY CaMKII
VELEZ RUEDA J.O.; PINILLA A.; MATTIAZZI A.R.; PALOMEQUE J
Congreso; Encuentro internacional de la ISHR; 2010
We recently described that angiotensin II (AngII)-induced apoptosis in vitro is mediated by Ca2+-calmodulin-dependent protein kinase II (CaMKII). In a further step, our aim was to establish whether the endogenous production of Ang II in vivo induces apoptosis through CaMKII. For this purpose we used a rat heart failure model induced by high doses of Isoproterenol (Iso rats) and Spontaneously Hypertensive Rats (SHR), a strain with elevated AngII plasma levels. After 1 month of treatment Iso rats showed 130.9±33.5% increase in aldosterone serum levels (an index of the renin-angiotensin system activity), an increase in blood pressure (19.4±6.6%), heart hypertrophy (left ventricular mass index , 12.8±0.6 vs 16.0±0.4 mg/mm, control vs Iso rats) and apoptosis (3-fold increase of TUNEL positive nuclei, and significant increase in caspase-3 activity and Bax/Bcl2) associated with a significant increase in P-CaMKII (91.1±0.8%) and in P-Thr17 of phospholamban, a direct substrate of CaMKII. The SHR also showed an increase in blood pressure (85.7±4.5%), heart hypertrophy (LVMI 13.2±1.13 vs 20.5±1.0, control vs Iso rats) and apoptosis (caspasa & Bax/Bcl-2) associated with an increase in CaMKII activity (P-CaMKII and P-Thr17) with respect to controls. Treatment of SHR for 1 month with a non-antihypertensive dose of enalapril significantly decreases both apoptosis and CaMKII activity. These results might suggest that endogenous increases in AngII serum levels could induce apoptosis in vivo through a CaMKII-dependent pathway.