Thesis defense Amandine Vergnaud

Equipe

Team II - Ion channels and cardiopathies

Directeur de thèse

Benjamin Lauzier
 

Co-Encadrante

Manon Denis

Rapporteurs

Caroline Cieniewski-Bernard, PhD, MCU, Université de Lille
Stéphane Zaffran, PhD, DR, INSERM, Marseille Medical Genetics

Examinateurs

Claire Arnaud, PharmD,PhD, DR, Docteur en pharmacie, Laboratoire HP2, Université Grenoble Alpes
Bruno Lefort, MD, PhD, PUPH, CHU Tours

Abstract

O-GlcNAcylation, a post-translational modification that plays a role in a multitude of cellular processes, is regulated by two enzymes: O-GlcNAcase (OGA), and O-GlcNAc transferase (OGT), which remove and adds moiety. Cardiac OGT KO results in developmental defects in the heart and elevation of O-GlcNAcylation are associated with cardiomyocyte hypertrophy. The objective is to study the effect of hyper O-GlcNAcylation on cardiac development. Female Wistar rats were administered a daily subcutaneous injection of NButGT (10 mg/kg) to increase the levels of O-GlcNAc beginning on the day prior to mating and continuing throughout the duration of pregnancy. Foetus were collected at 15.5 and 20.5 days post-mating (E15.5, E20.5), at birth (D0), 28 days (D28) and 84 days after birth (D84). Morphological and histological analyses of cardiac and body development were conducted. Echocardiography was done at birth and D28. 3'RNA sequencing and O-GlcNAcylomics study were This study proves that increase O-GlcNAc during development affects global growth with impact on heart. O-GlcNAcylomic and transcriptomic approach allow us to identify protein of interest. Given the strong link between O-GlcNAc and diabetes these results may offer novel insights into potential strategies for preventing cardiac hypertrophy in newborns of diabetic mothers.