Frontiers in Cardiovascular Medicine (Oct 2024)

Inhibition of angiogenesis and regenerative lung growth in Lepob/ob mice through adiponectin-VEGF/VEGFR2 signaling

  • Tendai Hunyenyiwa,
  • Tendai Hunyenyiwa,
  • Priscilla Kyi,
  • Priscilla Kyi,
  • Mikaela Scheer,
  • Mrudula Joshi,
  • Mrudula Joshi,
  • Mario Gasparri,
  • Tadanori Mammoto,
  • Tadanori Mammoto,
  • Akiko Mammoto,
  • Akiko Mammoto

DOI
https://doi.org/10.3389/fcvm.2024.1491971
Journal volume & issue
Vol. 11

Abstract

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IntroductionObesity 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.MethodsUnilateral PNX is performed on Lepob/ob obese mice to examine vascular and alveolar regeneration.ResultsRegenerative lung growth and expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR2 induced after PNX are inhibited in Lepob/ob obese mice. The levels of adiponectin that exhibits pro-angiogenic and vascular protective properties increase after unilateral PNX, while the effects are attenuated in Lepob/ob 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 Lepob/ob obese mice.DiscussionThese 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.

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