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肺静脉内皮细胞的动态行为和谱系可塑性。

Dynamic behavior and lineage plasticity of the pulmonary venous endothelium.

作者信息

Wong Joanna, Zhao Gan, Adams-Tzivelekidis Stephanie, Wen Hongbo, Chandrasekaran Prashant, Michki Sylvia N, Gentile Maria E, Singh Madeline, Kass-Gergi Sara, Mendoza Meryl, Holcomb Nicolas P, Li Xinyuan, Tang Alan T, Negretti Nicholas M, Sucre Jennifer M S, Frank David B, Vaughan Andrew E

机构信息

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Nat Cardiovasc Res. 2024 Dec;3(12):1584-1600. doi: 10.1038/s44161-024-00573-2. Epub 2024 Dec 9.

DOI:10.1038/s44161-024-00573-2
PMID:39653825
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12035778/
Abstract

Repair of the pulmonary vascular bed and the origin of new vasculature remain underexplored despite the critical necessity to meet oxygen demands after injury. Given their critical role in angiogenesis in other settings, we investigated the role of venous endothelial cells in endothelial regeneration after adult lung injury. Here we identified Slc6a2 as a marker of pulmonary venous endothelial cells and generated a venous-specific, inducible Cre mouse line. We observed that venous endothelial cells proliferate into the adjacent capillary bed upon influenza injury and hyperoxia injury. Imaging analysis demonstrated that venous endothelial cells proliferate and differentiate into general capillary and aerocyte capillary endothelial cells after infection, thus contributing to repair of the capillary plexus vital for gas exchange. Our studies thus establish that venous endothelial cells exhibit demonstrable progenitor capacity upon respiratory viral injury and sterile injury, contributing to repair of the alveolar capillary bed responsible for pulmonary function.

摘要

尽管在损伤后满足氧气需求至关重要，但肺血管床的修复和新血管的起源仍未得到充分研究。鉴于静脉内皮细胞在其他情况下对血管生成的关键作用，我们研究了成年肺损伤后静脉内皮细胞在内皮再生中的作用。在这里，我们确定Slc6a2为肺静脉内皮细胞的标志物，并生成了一种静脉特异性、可诱导的Cre小鼠品系。我们观察到，在流感损伤和高氧损伤后，静脉内皮细胞会增殖进入相邻的毛细血管床。成像分析表明，感染后静脉内皮细胞会增殖并分化为普通毛细血管和肺泡细胞毛细血管内皮细胞，从而有助于修复对气体交换至关重要的毛细血管丛。因此，我们的研究表明，在呼吸道病毒损伤和无菌损伤后，静脉内皮细胞表现出明显的祖细胞能力，有助于修复负责肺功能的肺泡毛细血管床。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35e0/12035778/0e5ed6a2410e/nihms-2072156-f0008.jpg
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