High-Fat Diet Attenuates the Improvement of Hypoxia-induced Pulmonary Artery Hypertension in Mice During Reoxygenation.

Abstract

Background: It has been widely recognized that metabolic disorder is associated with pulmonary hypertension. It is known that elevated pulmonary artery pressure induced by hypoxia in mice returns to normal pressure under reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of a high-fat diet (HFD) on the decrease of pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced pulmonary hypertension.Methods: We used female C57/Bl6 mice aged 8 weeks. After the mice were exposed to hypoxia (10% oxygen for 4 weeks) for induction of pulmonary hypertension. Then, they were returned to normoxic conditions and randomized into a normal diet (ND) group and a HFD group. Both groups were fed their respective diets for 12 weeks.Results: The right ventricular systolic pressure measured by a micro-manometer catheter and the Fulton index were significantly higher in the HFD group than in the ND group at 12 weeks after reoxygenation. The medial smooth muscle area was larger in the HFD group. Caspase 3 activity in lung tissue of the HFD group was decreased, and an apoptosis of pulmonary smooth muscle cells was suppressed after reoxygenation. Moreover, the expression levels of peroxisome proliferator-activated receptor-γ and apelin were lower in the HFD group than in the LFD group.Conclusion: Our results suggest the metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced pulmonary hypertension under reoxygenation.