Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.

Autor:	Arolkar G; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India (G.A., S.K.K., S.K., B.B., S.D.)., Kumar SK; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India (G.A., S.K.K., S.K., B.B., S.D.)., Wang H; Department of Cardiothoracic Surgery (H.W., Y.J.W.), Stanford University School of Medicine, CA., Gonzalez KM; Institute for Stem Cell Biology and Regenerative Medicine (K.M.G., K.R.-H.), Stanford University School of Medicine, CA.; Department of Biology (K.M.G., K.R.-H.), Stanford University, CA., Kumar S; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India (G.A., S.K.K., S.K., B.B., S.D.)., Bishnoi B; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India (G.A., S.K.K., S.K., B.B., S.D.)., Rios Coronado PE; Department of Bioengineering (P.E.R.C.), Stanford University, CA., Woo YJ; Department of Cardiothoracic Surgery (H.W., Y.J.W.), Stanford University School of Medicine, CA., Red-Horse K; Institute for Stem Cell Biology and Regenerative Medicine (K.M.G., K.R.-H.), Stanford University School of Medicine, CA.; Department of Biology (K.M.G., K.R.-H.), Stanford University, CA.; Howard Hughes Medical Institute, Chevy Chase, MD (K.R.-H.)., Das S; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, India (G.A., S.K.K., S.K., B.B., S.D.).
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2023 Aug; Vol. 43 (8), pp. 1455-1477. Date of Electronic Publication: 2023 Jun 22.
DOI:	10.1161/ATVBAHA.123.319319
Abstrakt:	Background: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. Methods: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. Results: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. Conclusions: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate. Competing Interests: Disclosures None.
Databáze:	MEDLINE
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