Abstract : The prevalence of obesity follows a progression without precedent in the industrialized countries and increases the cardiovascular morbimortality dramatically. The excessive development of adipocyte has a direct impact on heart through peptides and cytokines which it secretes and an indirect impact through the increase in the volemy. These changes induce modifications of the gene expression in the cardiomyocytes and fibroblasts. For example, the expression of the muscarinic M2 receptor decreases in the right atria from obese and hypertensive dogs.
In this canine model, we showed in the M2/eNOS pathway that there were compensatory regulations at the level of the eNOS. We also showed that the adrenomedullin, peptide implied in pressure homeostasis and secreted by adipocytes, determines the compensatory surexpression of the M2 receptor, in the model of P19 cardiomyocytes lines.
We undertook a general study on the level of the transcriptome with the aim to identify the whole of the modifications induced in the obese heart. These studies, in the model of hypertensive obese dog, then at Man showed that the heart of obese modified the expression of its genes and that it had a particular transcriptional profile. These regulations converge towards TGF beta and Wnt pathways, both normally implied in the cardiogenesis. Lastly, this work initiated the unknown new gene study (PPR1 & PPR2).