Obesity in Vascular and Alveolar Morphogenesis after Pneumonectomy

Abstract

Obese population is rapidly growing worldwide. Obesity is associated with chronic lung diseases including chronic obstructive pulmonary disease (COPD). Impairment of lung regeneration and repair contributes to the pathogenesis of COPD. Angiogenesis – the formation of new blood capillaries ‐ plays a key role in organ regeneration. Inhibition of angiogenesis attenuates lung growth after unilateral pneumonectomy (PNX) and obesity is accompanied by endothelial cell (EC) dysfunction. However, the effects of obesity on lung vascular and alveolar regeneration remain unclear. Compensatory lung growth and vascular and alveolar morphogenesis after PNX are suppressed in leptin‐deficient ob/ob mice treated with high‐fat diet compared to that in control lean mice. The levels of the major angiogenic factor, vascular endothelial growth factor (VEGF) are higher in the serum and the brown adipose tissue collected from post‐PNX mice compared to those from sham‐operated control mice, while these effects are attenuated in post‐PNX leptin‐deficient ob/ob mice with high‐fat diet. The serum collected from post‐PNX control mice stimulates EC sprouting, while EC sprouting is inhibited when treated with serum collected from leptin‐deficient ob/ob mice after PNX. These results suggest that obesity may inhibit post‐PNX regenerative lung growth through VEGF signaling. Modulation of VEGF signaling may be the efficient strategy to restore lung regeneration and repair in obese population.Support or Funding InformationNIH R01HL142578