RT Journal Article T1 Capillary pruning couples tissue perfusion and oxygenation with cardiomyocyte maturation in the postnatal mouse heart A1 Santamaría, Ricardo A1 Cruz-Caballero, Javier A1 Gkontra, Polyxeni A1 Jiménez-Montiel, Alberto A1 Clemente, Cristina A1 López, Juan A. A1 Vázquez, Jesús A1 Hutloff, Andreas A1 Lara-Pezzi, Enrique A1 Arroyo, Alicia G. A1 Villalba Orero, María AB Introduction: Removal of poorly perfused capillaries by pruning contributes to remodeling the microvasculature to optimize oxygen and nutrient delivery. Blood flow drives this process by promoting the intravascular migration of endothelial cells in developing networks, such as in the yolk sac, zebrafish brain or postnatal mouse retina. Methods: In this study, we have implemented innovative tools to recognize capillary pruning in the complex 3D coronary microvasculature of the postnatal mouse heart. We have also experimentally tested the impact of decreasing pruning on the structure and function of this network by altering blood flow with two different vasodilators: losartan and prazosin. Results: Although both drugs reduced capillary pruning, a combination of experiments based on ex vivo imaging, proteomics, electron microscopy and in vivo functional approaches showed that losartan treatment resulted in an inefficient coronary network, reduced myocardial oxygenation and metabolic changes that delayed the arrest of cardiomyocyte proliferation, in contrast to the effects of prazosin, probably due to its concomitant promotion of capillary expansion. Discussion: Our work demonstrates that capillary pruning contributes to proper maturation and function of the heart and that manipulation of blood flow may be a novel strategy to refine the microvasculature and improve tissue perfusion after damage. PB Frontiers Media SA SN 2296-634X YR 2023 FD 2023-11-07 LK https://hdl.handle.net/20.500.14352/97905 UL https://hdl.handle.net/20.500.14352/97905 LA eng NO European Regional Development Fund NO Deutsche Forschungsgemeinschaft NO MICINN NO Comunidad de Madrid NO Fundación “La Caixa” NO FPI Severo Ochoa NO Severo Ochoa Center of Excellence DS Docta Complutense RD 13 abr 2025