Molecular basis and key biological processes for myocardial regeneration: Transcriptomic analysis of acute myocardial infarction in a translational ovine model

Background: Recently, transcriptomic analysis has been key in identifying therapeutic targets in cardiovascular regeneration. The postnatal loss of cardiomyocyte proliferative capacity has been linked to the transition from glycolysis to fatty acid oxidation in rodent models of acute myocardial infarction (AMI). However, the transcriptomic profile of these processes in large mammals more similar to humans is still unknown. The aim of this study was to examine the transcriptomic profile, from the proliferative fetal stage to the non-regenerative infarcted adult stage, in an ovine AMI model. Methods: Samples consisted of fetal sheep hearts sequenced in our laboratory and adult sheep hearts (healthy, infarct, and infarct border) from the Gene Expression Omnibus repository (GSE164245). Results: Fetal tissue showed changes in epigenetic regulation and a predominance of glycolytic metabolism, whereas in the adult infarct core and border zones, there was a partial activation of glycolysis and a reduction in the expression of genes associated with beta-oxidation of fatty acids. Myocardial infarction in adult sheep triggers metabolic changes that partially mimic fetal regenerative processes. Conclusions: These findings will allow for a more precise understanding of the mechanisms underlying cardiac regeneration and facilitate the translation of regenerative therapies for clinical application in humans.