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. , 13-16 Mayo 2010, Kyoto, Japón
PALOMEQUE J ; VELEZ RUEDA O; PINILLA OA; MATTIAZZI A
Congreso; Congreso Mundial 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 AngII, in vivo, induces apoptosis through CaMKII. For this purpose we used Spontaneously Hypertensive Rats (SHR), a strain with elevated AngII levels and a heart failure model induced by high doses of Isoproterenol (Iso rats). SHR showed an increase in blood pressure (85.7±4.5%), heart hypertrophy (left ventricular mass index [LVMI] 13.2±1.1 vs 20.5±1.0 mg/mm, control vs SHR) and apoptosis (49.4±14.2% increase in caspase-3) associated with an increase in CaMKII activity (177.6±77.5% in P-CaMKII and 108.4±35.8% in P-Thr17 of phospholamban, a direct substrate of CaMKII) with respect to controls. Treatment of SHR for 1 month with a non-antihypertensive dose of enalapril significantly decreased both apoptosis and CaMKII activity. Similarly, 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 (LVMI 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. Taken together, the results suggest that endogenous increases in AngII serum levels induce apoptosis in vivo via a CaMKII-dependent pathway.