Capillary Pruning Couples Tissue Perfusion and Oxygenation with Cardiomyocyte Maturation in the Postnatal Mouse Heart

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2023 Nov 29

PMID 38020883

Authors

Ricardo Santamaria

Javier Cruz-Caballero

Polyxeni Gkontra

Alberto Jimenez-Montiel

Cristina Clemente

Juan A Lopez

Maria Villalba-Orero

Jesus Vazquez

Andreas Hutloff

Enrique Lara-Pezzi

Alicia G Arroyo

Affiliations

Soon will be listed here.

Abstract

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. 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. Although both drugs reduced capillary pruning, a combination of experiments based on imaging, proteomics, electron microscopy and 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. 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.

Citing Articles

In Vitro Model of Vascular Remodeling Under Microfluidic Perfusion.

Nishikata K, Doi K, Kaneoya N, Nakamura M, Futai N Micromachines (Basel). 2025; 16(1).

PMID: 39858670 PMC: 11767722. DOI: 10.3390/mi16010014.

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