The specific inhibition of the cardiac electrogenic sodium/bicarbonate cotransporter leads to cardiac hypertrophy

DI MATTÍA RA; JAQUENOD DE GIUSTI, C; BLANCO P; PORTIANSKY E; AIELLO EA; ORLOWSKI A

Virtual

Congreso; SCHCF + ALACF 2020 joint meeting; 2020

Introduction: The Na+/HCO3- cotransporter (NBC) is one of the main alkalinizing transporters of the cardiomyocytes. There aretwo isoforms of NBC: the electrogenic NBCe1 and the electroneutral NBCn1. Although both isoforms enters Na+ into the cell,NBCe1 contributes with half of Na+ per HCO3-, evidencing a better efficiency. We have previously found a reduction of NBCe1activity together with an increased NBCn1 activity in cardiac hypertrophy (CH) models. Aims: We developed an interference RNAcloned in a cardiotropic adeno-associated vector (AAV9-shNBCe1) to study the effect of the specific inhibition of NBCe1 in CH.Methodology: We delivered the virus through a lateral tail vein injection in 3 months old male Wistar rats and then performed aseries of studies to assess CH, using an AAV9-shControl as control. Data were expressed as means±S.E.M. and compared withStudent´s t-test or two-way ANOVA. The experimental protocol was approved by the Animal Welfare Committee of La Plata Schoolof Medicine. Results: After 30 days of injection, we confirm a significant reduction on NBCe1 ventricular expression. In addition,we found an increase in left ventricular mass index obtained by echocardiography on hearts injected with AAV9-shNBCe1 (AAV9-shControl: 1.01±0.1; n=11; AAV9-shNBCe1*: 1.46±0.11, n=11; *p