CIC   05421
CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Successive activation of PKA and CaMKII pathways in the progression towards left ventricular hypertrophy (LVH) and heart failure (HF)
Autor/es:
BECERRA R; GONULENKO R; SAID M; RINALDI G; MUNDIÑA WEILEWNMAN C; VITTONE L; MATTIAZZI A
Lugar:
Ciudad Autónoma de Buenos Aires - Buenos Aires - Argentina
Reunión:
Congreso; XVII Meeting of ISHR Latin American Section; 2009
Institución organizadora:
ISHR sección Latinoamericana
Resumen:
Alterations of sympathetic tone and Cai2+ homeostasis occur in the progression towards LVH and HF. We studied the expression and phosphorylation of proteins that regulate Cai2+ and cardiac function in rats after 3, 5 and 9 months (mo) of aortic constriction (AC). AC rats were compared with the corresponding sham (S). At 3 months, systolic and diastolic LV function decreased: maximum rate of pressure development was (mmHg/s) 4478±228 AC vs. 5581± 416 S (n=7–9) (pb0.05) and relaxation constant Tau (ms) was 13.6±1.1 AC vs. 8.4±0.8 S (n=7–8) (pb0.05). LV function transiently mproved (5 months) in association with an increase in PKA-dependent phosphorylation of phospholamban (PLN), the regulatory protein of SERCA2a. At 9 months, LVH (LV weight/corporal weight) was evident 2.21±0.06 AC vs. 1.99±0.04 S (n=5–6) (pb0.05), in association with an impairment in contractility, an increase in end diastolic pressure and an enhanced CaMKII-dependent phosphorylation of PLN. The expression of Na+/Ca2+ exchanger, SERCA2a, PLN and ryanodine receptors did not change. Results suggest that in the progression towards LVH and HF there is a change in the signaling pathways that modulate LV function. While activation of PKA is associated to beneficial effects, activation of CaMKII is associated with a severe impairment of LV function.
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