DECREASED CA2+ LEAK FROM THE SARCOPLASMIC RETICULUM (RS) PROTECTS FROM EARLY DEVELOPMENT OF PATHOLOGICAL CARDIAC HYPERTROPHY

SAPIA, LUCIANA; DIAZ-ZEGARRA, LEANDRO A.; VALVERDE, CARLOS A; VÉLEZ-RUEDA, J OMAR; ROSSETTI, NOELIA; AIELLO, ERNESTO A.; DE GIUSTI, VERÓNICA; CELY ORTIZ, D.C. ALEJANDRA; BLANCO, PAULA; MATTIAZZI, RAMONA ALICIA

Virtual

Congreso; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2020; 2020

SAIC-SAI-SAFIS

Abnormal Ca2+ release from the SR, associated with Ca2+-calmodulin kinase II (CaMKII)-dependent phosphorylation of RyR2 at Ser2814, has been linked to cardiac diseases, such as pathological cardiac hypertrophy (PCH) and its progression to heart failure.The increase in SR Ca2+ uptake by phospholamban (PLN) ablation (PLNKO), to restore the decrease in SR Ca2+ load produced by RyR2 phosphorylation, ameliorates SR Ca2+ handling but exacerbates cardiac disease.In the present study, we tested the hypothesis that the abrogation of CaMKII-induced Ca2+ loss by RyR2, induced by CaMKII phosphorylatable site mutation (S2814A), protects the heart from RS Ca2+ overload produced by PLN ablation and delays the development ofPCH.We used hearts from 10 weeks old WT, S2814A, PLNKO mice and a crossbreed strain of S2814A and PLNKO generated in our laboratory, named SAKO. WT and SAKO strain were subjected to transverse aortic constriction (TAC), an experimental surgical model for pressure overload-induced PCH, known to be associated with CaMKII overexpression.Cardiac hypertrophy parameters (transthoracic echocardiography) were studied one month after the intervention. SAKO mice were monitored up to 180 days.*p