@article {157493, title = {Artery regeneration: Molecules, mechanisms and impact on organ function.}, journal = {Semin Cell Dev Biol}, volume = {171}, year = {2025}, month = {2025 May 02}, pages = {103611}, abstract = {

Replenishment of artery cells to repair or create new arteries is a promising strategy to re-vascularize ischemic tissue. However, limited understanding of cellular and molecular programs associated with artery (re-)growth impedes our efforts towards designing optimal therapeutic approaches. In this review, we summarize different cellular mechanisms that drive injury-induced artery regeneration in distinct organs and organisms. Artery formation during embryogenesis includes migration, self-amplification, and changes in cell fates. These processes are coordinated by multiple signaling pathways, like Vegf, Wnt, Notch, Cxcr4; many of which, also involved in injury-induced vascular responses. We also highlight how physiological and environmental factors determine the extent of arterial re-vascularization. Finally, we discuss different in vitro cellular reprogramming and tissue engineering approaches to promote artery regeneration, in vivo. This review provides the current understanding of endothelial cell fate reprogramming and explores avenues for regenerating arteries to restore organ function through efficient revascularization.

}, keywords = {Artery; Cellular reprogramming; Collateral arteries; Development; Endothelial cells; Genetic lineage tracing; Regeneration.}, issn = {1096-3634}, doi = {10.1016/j.semcdb.2025.103611}, url = {https://www.sciencedirect.com/science/article/pii/S1084952125000217?via\%3Dihub}, author = {Ghosh, Swarnadip and Bishnoi, Bhavnesh and Das, Soumyashree} } @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 {150945, title = {Specialized post-arterial capillaries facilitate adult bone remodelling.}, journal = {Nat Cell Biol}, year = {2024}, month = {2024 Nov 11}, abstract = {

The vasculature of the skeletal system is crucial for bone formation, homoeostasis and fracture repair, yet the diversity and specialization of bone-associated vessels remain poorly understood. Here we identify a specialized type of post-arterial capillary, termed type R, involved in bone remodelling. Type R capillaries emerge during adolescence around trabecular bone, possess a distinct morphology and molecular profile, and are associated with osteoprogenitors and bone-resorbing osteoclasts. Endothelial cell-specific overexpression of the transcription factor DACH1 in postnatal mice induces a strong increase in arteries and type R capillaries, leading to local metabolic changes and enabling trabecular bone formation in normally highly hypoxic areas of the diaphysis. Indicating potential clinical relevance of type R capillaries, these vessels respond to anti-osteoporosis treatments and emerge during ageing inside porous structures that are known to weaken compact bone. Our work outlines fundamental principles of vessel specialization in the developing, adult and ageing skeletal system.

}, issn = {1476-4679}, doi = {10.1038/s41556-024-01545-1}, author = {Mohanakrishnan, Vishal and Sivaraj, Kishor K and Jeong, Hyun-Woo and Bovay, Esther and Dharmalingam, Backialakshmi and Bixel, M Gabriele and Dinh, Van Vuong and Petkova, Milena and Paredes Ugarte, Isidora and Kuo, Yi-Tong and Gurusamy, Malarvizhi and Raftrey, Brian and Chu, Nelson Tsz Long and Das, Soumyashree and Rios Coronado, Pamela E and Stehling, Martin and S{\"a}vendahl, Lars and Chagin, Andrei S and M{\"a}kinen, Taija and Red-Horse, Kristy and Adams, Ralf H} } @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} } @article {90470, title = {New Research Is Shining Light on How Collateral Arteries Form in the Heart: a Future Therapeutic Direction?}, journal = {Curr Cardiol Rep}, volume = {23}, year = {2021}, month = {2021 Mar 02}, pages = {30}, abstract = {

PURPOSE OF REVIEW: Collateral arteries create artery-artery anastomoses that could serve as natural bypasses that in the heart could relieve the various complications of ischemia heart disease. Recent work using animal models have begun to reveal details of how coronary collateral arteries form.

RECENT FINDINGS: Mouse genetics has been used to study the cellular and molecular mechanisms of collateral artery development. Collateral arteries are not pre-existing in the mouse heart, and only form in response to injury. Myocardial infarction creates tissue hypoxia that triggers the expression of growth factors and chemokines that guide collaterogenesis. Collateral development is more robust in neonatal hearts when compared with adults, and contributes to neonatal heart regeneration. The identification of signaling pathways and cellular responses underlying coronary collateral artery development suggests potential translational strategies. Continued investigation into this subject could lead to the identification of targetable pathways that induce collateral arteries for cardiac revascularization.

}, issn = {1534-3170}, doi = {10.1007/s11886-021-01460-z}, author = {Red-Horse, Kristy and Das, Soumyashree} }