@article {149384, title = {Development of pial collaterals by extension of pre-existing artery tips.}, journal = {Cell Rep}, volume = {43}, year = {2024}, month = {2024 Sep 24}, pages = {114771}, abstract = {

Pial collaterals provide protection from ischemic damage and improve the prognosis of stroke patients. The origin or precise sequence of events underlying pial collateral development is unclear and has prevented clinicians from adapting new vascularization and regeneration therapies. We use genetic lineage tracing and intravital imaging of mouse brains at cellular resolution to show that during embryogenesis, pial collateral arteries develop from extension and anastomoses of pre-existing artery tips in a VegfR2-dependent manner. This process of artery tip extension occurs on pre-determined microvascular tracks. Our data demonstrate that an arterial receptor, Cxcr4, earlier shown to drive artery cell migration and coronary collateral development, is dispensable for the formation and maintenance of pial collateral arteries. Our study shows that collateral arteries of the brain are built by a mechanism distinct from that of the heart.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2024.114771}, author = {Kumar, Suraj and Ghosh, Swarnadip and Shanavas, Niloufer and Sivaramakrishnan, Vinayak and Dwari, Manish and Das, Soumyashree} } @article {130548, title = {Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.}, journal = {Arterioscler Thromb Vasc Biol}, year = {2023}, month = {2023 Jun 22}, abstract = {

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.

}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.123.319319}, author = {Arolkar, Gauri and Krishna Kumar, Sneha and Wang, Hanjay and Gonzalez, Karen M and Kumar, Suraj and Bishnoi, Bhavnesh and Rios Coronado, Pamela E and Woo, Y Joseph and Red-Horse, Kristy and Das, Soumyashree} }