Pulmonary vascular endothelial cells could contribute to maintain homeostasis in adult lung vasculature. “Tissue-resident” endothelial progenitor cells (EPCs) play pivotal roles in postnatal vasculogenesis, vascular repair, and tissue regeneration; however, their local pulmonary counterparts remain to be defined. To determine whether prominin-1/CD133 expression can be a marker of tissue-resident vascular EPCs in the pulmonary circulation, we examined the origin and characteristics of prominin-1/CD133-positive (Prom1+) PVECs considering cell cycle status, viability, histological distribution, and association with pulmonary vascular remodeling. Prom1+ PVECs exhibited high steady-state transit through the cell cycle compared with Prom1− PVECs and exhibited homeostatic cell division as assessed using the label dilution method and mice expressing green fluorescent protein. In addition, Prom1+ PVECs showed more marked expression of putative EPC markers and drug resistance genes as well as highly increased activation of aldehyde dehydrogenase compared with Prom1− PVECs. Bone marrow reconstitution demonstrated that tissue-resident cells were the source of >98% of Prom1+ PVECs. Immunofluorescence analyses revealed that Prom1+ PVECs preferentially resided in the arterial vasculature, including the resistant vessels of the lung. The number of Prom1+ PVECs was higher in developing postnatal lungs. Sorted Prom1+ PVECs gave rise to colonies and formed fine vascular networks compared with Prom1− PVECs. Moreover, Prom1+ PVECs increased in the monocrotaline and the Su-5416 + hypoxia experimental models of pulmonary vascular remodeling. Our findings indicated that Prom1+ PVECs exhibited the phenotype of tissue-resident EPCs. The unique biological characteristics of Prom1+ PVECs predominantly contribute to neovasculogenesis and maintenance of homeostasis in pulmonary vascular tissues.
- pulmonary vascular endothelial cells
- pulmonary vascular remodeling
- Copyright © 2016 the American Physiological Society
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