Hunyenyiwa Tendai, Kyi Priscilla, Scheer Mikaela, Joshi Mrudula, Gasparri Mario, Mammoto Tadanori, Mammoto Akiko
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, United States.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, United States.
Front Cardiovasc Med. 2024 Oct 16;11:1491971. doi: 10.3389/fcvm.2024.1491971. eCollection 2024.
Obesity is associated with impairment of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in regenerative lung growth after unilateral pneumonectomy (PNX). We have reported that obesity inhibits angiogenesis. The effects of obesity on post-PNX lung vascular and alveolar regeneration remain unclear.
Unilateral PNX is performed on obese mice to examine vascular and alveolar regeneration.
Regenerative lung growth and expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 induced after PNX are inhibited in obese mice. The levels of adiponectin that exhibits pro-angiogenic and vascular protective properties increase after unilateral PNX, while the effects are attenuated in obese mice. Post-PNX regenerative lung growth and increases in the levels of VEGF and VEGFR2 are inhibited in adiponectin knockout mice. Adiponectin stimulates angiogenic activities in human lung endothelial cells (ECs), which is inhibited by decreasing the levels of transcription factor Twist1. Adiponectin agonist, AdipoRon restores post-PNX lung growth and vascular and alveolar regeneration in obese mice.
These findings suggest that obesity impairs lung vascular and alveolar regeneration and adiponectin is one of the key factors to improve lung regeneration in obese people.
肥胖与伤口愈合和组织再生受损有关。血管生成，即新毛细血管的形成，在单侧肺切除术后（PNX）的肺再生生长中起关键作用。我们已经报道肥胖会抑制血管生成。肥胖对PNX后肺血管和肺泡再生的影响尚不清楚。
对肥胖小鼠进行单侧PNX，以检查血管和肺泡再生情况。
PNX后诱导的肺再生生长以及血管内皮生长因子（VEGF）及其受体VEGFR2的表达在肥胖小鼠中受到抑制。具有促血管生成和血管保护特性的脂联素水平在单侧PNX后升高，而在肥胖小鼠中这种作用减弱。在脂联素基因敲除小鼠中，PNX后的肺再生生长以及VEGF和VEGFR2水平的升高受到抑制。脂联素刺激人肺内皮细胞（ECs）的血管生成活性，而降低转录因子Twist1的水平会抑制这种活性。脂联素激动剂AdipoRon可恢复肥胖小鼠PNX后的肺生长以及血管和肺泡再生。
这些发现表明肥胖会损害肺血管和肺泡再生，而脂联素是改善肥胖人群肺再生的关键因素之一。
