Deciphering the potency of ventricular trabeculae to repair the heart during cardiac regeneration in the mouse

Abstract

The mammalian heart can regenerate only during a short period of time after birth which coincides with the maturation of the myocardial wall though compaction of the ventricular trabeculae. During embryonic development, trabeculae are transient myocardial invaginations at the inner ventricular surface. Genetic tracing analyses show that trabeculae give rise to conductive and contractile cardiomyocytes and participate in the development of the inner half of the ventricular wall and to the ventricular conductive system (VCS). We hypothesize that ventricular trabeculae possess superior regenerative capacities compared to compact myocardium. To investigate the contribution of ventricular trabeculae and the maturation of the VCS during cardiac regeneration after neonatal myocardial infarction (MI). Neonatal MI was performed by the permanent ligation of the left coronary artery on one day-old mice. Genetic tracing analysis combined with immunofluorescence both on section and cleared organ were used to followed trabecular-derived cells. After a labeling at fetal stage, numerous trabecular-derived cells participate to the regeneration of the myocardial wall; however, they don’t show any clonal expansion. During the first week after injury, a large scar forms and the VCS is damaged when the scar reaches the subendocardial zone. Three weeks after injury, VCS defects remain in several hearts with a localized gap in the Purkinje network. Moreover, we detect a dense network a of Purkinje fibers surrounding the ligation site suggesting an improper repair of the VCS during cardiac regeneration. These results show that ventricular trabeculae contribute partially to the regeneration of the myocardium after a neonatal MI in mice, suggesting other sources of cells to form new cardiomyocytes. In addition, our data show persistent defects in the VCS three weeks after injury while the ventricular wall is globally healthy.