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

DI MATTÍA RA; DIAZ ZEGARRA L; BLANCO P; PORTIANSKY E; VALVERDE CA; GONANO LA; JAQUENOD DE GIUSTI, C; AIELLO EA; ORLOWSKI A

Berlín

Congreso; XXIV World Congress International Society for Heart Research; 2022

Introduction: The Na+/HCO3- cotransporter (NBC) is one of the main alkalinizing transporters on cardiomyocytes. There are two isoforms of NBC: the electrogenic NBCe1 and the electroneutral NBCn1. Although both isoforms enter Na+ into the cell, NBCe1 contributes with half of Na+ per HCO3-, so it has a major efficiency. We have previously found a reduction of NBCe1 activity together with an increased NBCn1 activity in cardiac hypertrophy (CH) models.Objectives: We developed an interference RNA cloned in a cardiotropic adeno-associated viral vector (AAV9-shNBCe1) to study the effect of the specific inhibition of NBCe1 in CH.Materials & methods: We delivered the virus through a lateral tail vein injection in male 3 months old Wistar rats and then performed a series of studies to assess CH, using an AAV9-shControl as control. Data is expressed as means±S.E.M. and is compared with Student's t-test or two-way ANOVA test as needed. Results: After 30 days of injection, we detected a significant reduction on NBCe1 ventricular expression and activity. 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