Bmi1-Progenitor Cell Ablation Impairs the Angiogenic Response to Myocardial Infarction
Diego Herrero, Susana Cañón, Beatriz Pelacho, María Salvador-Bernáldez, Susana Aguilar, Cristina Pogontke, Rosa María Carmona, Jesús María Salvador, Jose María Perez-Pomares, Ophir David Klein, Felipe Prósper, Luis Jesús Jimenez-Borreguero, Antonio Bernad
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.