Impact of EPAC1 in cardiac calcium handling in aging

MARIÁNGELO JIE; FORMOSO K; DI MARZIO G.; MIALET J; SAID M; LEZOUALCH F; MUNDIÑA - WEILENMANN C

Congreso; XXVIII Congreso Argentino de Hipertensión Arterial (SAHA); 2022

Sociedad Argentina de Hipertension Arterial

Introduction: During aging, the reduced exercise tolerance and the decline of cardiac contraction is partly attributed to the β-adrenergic receptor desensitization and the reorganization of cAMP signalling. The major intracellular functions of cAMP are transduced by the protein kinase A and the Exchange Proteins directly Activated by cAMP (EPACs). A member of this family, EPAC1, has been involved in cardiac remodelling and diastolic calcium (Ca) leak from the sarcoplasmic reticulum in several cardiovascular diseases, but its role in cardiac aging has not been extensively studied. Aims: To study the impact of EPAC1 in cardiac Ca handling during aging.Methods: Intracellular Ca was assessed by confocal microscopy in cardiomyocytes isolated from adult (9 mo) and old (18 mo) WT or EPAC1 KO mice and loaded with Fluo-4. Myocytes were studied under basal conditions and after acute β-adrenergic stimulation with 100 M isoproterenol.Results: EPAC1 KO myocytes showed a decrease in Ca transient amplitude (CaT) at both ages (adult: 4.61±0.31 and 3.52±0.22 au; old: 4.38±0.16 and 3.62±0.17 au for WT and KO respectively, n= 16-26 myocytes for 3-4 mice in each group, p