Successive activation of PKA and CaMKII pathways in the progression towards left ventricular hypertrophy (LVH) and heart failure (HF)”

BECERRA R.V., GONULENKO R., SAID M. M., RINALDI G., MUNDIÑA- WEILENMANN C., VITTONE L., MATTIAZZI A.

Hotel Sheraton, Bs As, Argentina

Congreso; International Society for Heart Research, XVII Meeting Latin American Section; 2009

International Society for Heart Research, Latin American Section

Alterations of sympathetic tone and Ca2+i homeostasis occur in the progression towards LVH and HF. We studied the expression and phosphorylation of proteins that regulate Ca2+i 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 mo, systolic and diastolic LV function decreased: maximum rate of pressure development was (mmHg/sec) 4478±228 AC vs. 5581±416 S (n=7-9) (p<0.05) and relaxation constant Tau (msec) was 13.6±1.1 AC vs. 8.4±0.8 S (n=7-8) (p<0.05). LV function transiently improved (5 mo) in association with an increase in PKA-dependent phosphorylation of phospholamban (PLN), the regulatory protein of SERCA2a. At 9 mo, LVH (LV weigth/corporal weight) was evident 2.21±0.06 AC vs. 1.99±0.04 S (n=5-6) (p<0.05), 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.