Poster Session T - Cardiovascular Medicine and Research 3.
Vergnaud, Amandine, MSc
l'institut du thorax, INSERM UMR1087, CNRS UMR 6291, Univ Nantes
0695149438
amandine.vergnaud@univ-nantes.fr
Cardiac Morphological Alterations Associated With Hyper-O-GlcNAcylation Induced By Gestational Diabetes Are Independent Of Gender
A. Vergnaud1, L. Bergez1, M. Bouaud1, T. Dupas1, V. Aillerie1, A. Hivonnait1, A. Blangy--Letheule1, A. Erraud1, M. De Waard1, B. Rozec1, M. Denis1, B. Lauzier1
1: Université de Nantes, CHU Nantes, CNRS, INSERM, l’institut du thorax, F-44000 Nantes,
Poszter
Poster Session T - Cardiovascular Medicine and Research 3.
English
Cardiovascular Medicine and Research
Between 13 to 44% of pediatric hypertrophic cardiomyopathy cases are linked to poorly managed diabetes. Hyperglycemia is associated with an elevation in O-GlcNAcylation levels and aberrant cell proliferation. O-GlcNAcylation is a post-translational modification that plays a role in a number of cellular processes, including cell division and transcription. The regulation of O-GlcNAcylation is achieved through the action of a unique couple of enzymes the O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT) that respectively remove and add the moiety. A deletion of the OGT gene in the heart results in a defect in cardiac development. It is noteworthy that the OGT gene is located on the X chromosome, which could explain the observed differences in cardiac dysfunction between male and female. The objective of this study is to elucidate the influence of sex on the morphological alterations induced by O-GlcNAcylation during cardiac development.
Female rats were fed with High Fat High Sugar diet to induce gestational diabetes (HFHS) or with a control diet then from the day before mating till the end of pregnancy rats received a daily subcutaneous injection of NButGT (10mg/kg) to increase O-GlcNAc (NButGT) levels or Ringer Lactate (CTR/HFHS). Embryos were collected at 15.5 and 20.5 days after mating (E15.5, E20.5). A morphological analysis of cardiac and body development was realized. PCR was conducted to determine the sex.
NButGT increases O-GlcNAc levels in fetal hearts (E15.5, E20.5) with a ~1.5-fold increase. However, HFHS does not. Heart OGA and OGT expression is decreased in HFHS group compared to CTR group at E20.5. At both times, the increase in O-GlcNAc levels observed in NButGT group is associated with morphological alteration of embryo, it affects their weight(E15.5:CTR:271.9±6.3;NButGT:343.1±32.8;mg;p<0.05) and their height(E15.5:CTR:12.7±0.1;NButGT:14.2±0.3;mm;p<0.001). NButGT treatment also increases the ratio heart weight over embryo weight(E20.5:CTR:0.006±0.0002; NButGT:0.007±0.0002;p<0.5). The observed variations are independent of embryo sex.
Our study indicate that the stimulation of O-GlcNAcylation during development has a global impact on development, with a particular effect on the heart independently of the sex. The OGT gene is carried by the X chromosome, yet there is no discernible impact of the sex on OGT and OGA expression in our study group.
Nantes Université
Benjamin Lauzier
I do not give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
poszter
nem rendelkezett róla
7994
16:00
16:03