Bmi1-Progenitor cell ablation impairs the angiogenic response to myocardial infarction
Herrero, D.; Canon, S. ; Pelacho Samper, Beatriz
; Salvador-Bernaldez, M.; Aguilar, S.; Pogontke, C.; Carmona, R. M.; Salvador, J. M.; Perez-Pomares, J. M.; Klein, O. D.; Prosper Cardoso, Felipe
; Jimenez-Borreguero, L. J.; Bernad, A. (Autor de correspondencia)
Objective Cardiac progenitor cells reside in the heart in adulthood, although their physiological relevance remains unknown. Here, we demonstrate that after myocardial infarction, adult Bmi1(+) (B lymphoma Mo-MLV insertion region 1 homolog [PCGF4]) cardiac cells are a key progenitor-like population in cardiac neovascularization during ventricular remodeling.
Approach and Results These cells, which have a strong in vivo differentiation bias, are a mixture of endothelial- and mesenchymal-related cells with in vitro spontaneous endothelial cell differentiation capacity. Genetic lineage tracing analysis showed that heart-resident Bmi1(+) progenitor cells proliferate after acute myocardial infarction and differentiate to generate de novo cardiac vasculature. In a mouse model of induced myocardial infarction, genetic ablation of these cells substantially deteriorated both heart angiogenesis and the ejection fraction, resulting in an ischemic-dilated cardiac phenotype.
Conclusions These findings imply that endothelial-related Bmi1(+) progenitor cells are necessary for injury-induced neovascularization in adult mouse heart and highlight these cells as a suitable therapeutic target for preventing dysfunctional left ventricular remodeling after injury.