(687.16) Obesity in Angiogenesis and Lung Regeneration

Poster Board Number: D40

Tendai Hunyenyiwa (Medical College of Wisconsin), Priscilla Kyi (Medical College of Wisconsin), Kathryn Hendee (Medical College of Wisconsin), Kienna Matus (Medical College of Wisconsin), Tadanori Mammoto (Medical College of Wisconsin), Akiko Mammoto (Medical College of Wisconsin)

Obesity is associated with impairment of wound healing and tissue regeneration. Angiogenesis, the formation of new blood capillaries, plays a key role in organ regeneration and repair. We and other groups have reported that inhibition of angiogenesis attenuates lung growth after unilateral pneumonectomy (PNX) and that obesity is accompanied by endothelial cell dysfunction. The aim of this project is to investigate the effects of obesity on post-PNX lung vascular and alveolar morphogenesis. We have found that post-PNX regenerative lung growth is inhibited in Lepob/ob obese mice compared to Lepob/+ mice. The levels of the major angiogenic factor, vascular endothelial growth factor (VEGF) are higher in the serum and the lung tissue collected from post-PNX mice compared to those from sham-operated control mice, while these effects are attenuated in post-PNX Lepob/ob mice. The levels of adiponectin, one of the adipokines that exhibits pro-angiogenic and vascular protective properties, increase in the remaining mouse lungs after unilateral PNX, while these effects are attenuated in Lepob/ob obese mice. Regenerative lung growth, vascular and alveolar morphogenesis, and VEGF levels in the post-PNX mouse lungs are inhibited in adiponectin knockout mice. These results suggest that obesity inhibits post-PNX regenerative lung growth through adiponectin-VEGF signaling. Modulation of adiponectin-VEGF signaling may be the efficient strategy to restore lung regeneration and repair in obese people.

NIH R01HL139638, R01HL142578, and AHA 18TPA34170129