@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} }