Temporal and spatial dynamics in the regulation of myocardial metabolism during the ischemia-reperfusion process

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637 and CIBERCV16/11/00486) and Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008). Introduction In the context of severe myocardial ischemia, cardiac metabolism shifts from beta oxidation to glycolisis. However, the temporal and spatial dynamics of the main regulators of myocardial metabolism during the ischemia-reperfusion process in the infarcted heart has not been fully characterized. Methods Myocardial infarction (MI) was induced in swine by means of 90 minutes occlusion of the mid left anterior descending coronary artery using angioplasty balloons. Tetrazolium staining and intracoronary infusion of thioflavin-S were used to define the infarcted, adjacent, and remote areas. mRNA and protein expression of PGC1a, PPARa, ERRa, GLUT1, and GLUT4 were quantified in controls and in MI groups submitted to 48 hours and 3 weeks of reperfusion. Results Compared to controls, a severe and generalized drop of PGC1a mRNA gene and protein levels occurred in the infarcted, adjacent and remote areas since ischemia onset until 48 hours reperfusion that persists at 1 month in the infarcted region. Similar dynamics occurred in the infarcted, adjacent, and remote areas in the case of PPARa gene expresion; PPARa protein significantly decreased only until 48 hours reperfusion in the infarcted area. ERRa gene and protein expression persistenly decreased only in the infarcted region since ischemia onset until 1 month. Incrases in GLUT1 (since ischemia onset) and GLUT4 (at 1 month) were detected. Conclusions Dynamics and generalized changes in metabolism regulation to a shift from beta oxidation to glycolisis occur in the infarcted heart since ischemia onset until late after reperfusion. Further research in this field can be helpful for a better understanding of pathophysiology of myocardial infarction and to explore new therapeutic options.