Abstract 12990: High Fat Diet Delays Reverse Remodeling of Pulmonary Artery in Hypoxia-induced Pulmonary Hypertension Mice

Abstract

Background: Previous studies suggest the association of metabolic disorder with pulmonary hypertension. Elevated pulmonary artery pressure induced by hypoxia in mice returns to normal when they are placed back in normoxia. In this study, we investigated the effect of high-fat diet (HFD) on pulmonary artery pressure and reverse remodeling of pulmonary artery in mouse model of hypoxia-induced pulmonary hypertension. Methods: We used the female C57/Bl6 mice at the age of 8 weeks. After exposed to hypoxia (10% oxygen for 4 weeks) for induction of pulmonary hypertension, mice were returned to normoxic condition and fed HFD or low-fat diet (LFD) for 12 weeks. Results: The body weight (BW), glucose, low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C), but not triglyceride (TG) were significantly increased in HFD group (36.9±5.1 vs. 24.0±1.4 g [BW], P<0.05; 404.2±55.1 vs. 326.5±8.7 mg/dl [glucose], P<0.05; 10.2±3.6 vs. 7.5±0.9 mg/dl [LDL-C], P<0.05; 47.2±10.0 vs. 30.9±8.7 mg/dl [HDL-C], P<0.05 and 40.0±21.1 vs. 53.4±12.9 mg/dl [TG], P=0.09). The right ventricular systolic pressure (RVSP) measured by a micro-manometer catheter and the Fulton index in HFD group were significantly higher than those in LFD group (23.8±2.3 vs. 19.3±2.9 mmHg [RVSP], P<0.05; 0.30±0.06 vs. 0.25±0.04 [Fulton index], P<0.05, respectively). The medial smooth muscle area (expressed as a percentage of the external area of the vessel) was larger in HFD group (40.1±5.3 vs. 34.5±3.1%, P<0.05). In addition, the levels of active caspase-3 detected by Western blotting was lower in HFD group than in LFD group. TUNEL staining revealed that the apoptosis of pulmonary artery smooth muscle cells was suppressed in HFD group. Conclusion: Our results suggest that metabolic disorder attenuates pulmonary artery reverse remodeling, at least in part, by suppressing apoptosis of pulmonary artery smooth muscle cells when hypoxia-induced pulmonary hypertension mice were returned to normoxia.