Koichi Sugimoto1,2, Tetsuro Yokokawa3,4, Tomofumi Misaka3, Takashi Kaneshiro3, Akiomi Yoshihisa3, Kazuhiko Nakazato3, Yasuchika Takeishi3. 1. Department of Cardiovascular Medicine, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan. ksugi@fmu.ac.jp. 2. Department of Pulmonary Hypertension, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan. ksugi@fmu.ac.jp. 3. Department of Cardiovascular Medicine, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan. 4. Department of Pulmonary Hypertension, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan.
Abstract
BACKGROUND: It is widely recognized that metabolic disorder is associated with pulmonary hypertension (PH). It is known that hypoxia-induced elevated pulmonary artery pressure in mice returns to normal pressure during reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of high-fat diet (HFD) on the decrease in pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced PH. METHODS: We used female C57BL/6 mice aged 8 weeks. After being exposed to hypoxia (10% oxygen for four weeks) to induce PH, the mice were returned to normoxic conditions and randomized into a normal diet (ND) group and HFD group. Both groups were fed with their respective diets for 12 weeks. RESULTS: The Fulton index and right ventricular systolic pressure measured by a micro-manometer catheter 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 the lung tissue of the HFD group was decreased, and the 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 ND group. CONCLUSIONS: The results suggest that metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced PH during reoxygenation.
BACKGROUND: It is widely recognized that metabolic disorder is associated with pulmonary hypertension (PH). It is known that hypoxia-induced elevated pulmonary artery pressure in mice returns to normal pressure during reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of high-fat diet (HFD) on the decrease in pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced PH. METHODS: We used female C57BL/6 mice aged 8 weeks. After being exposed to hypoxia (10% oxygen for four weeks) to induce PH, the mice were returned to normoxic conditions and randomized into a normal diet (ND) group and HFD group. Both groups were fed with their respective diets for 12 weeks. RESULTS: The Fulton index and right ventricular systolic pressure measured by a micro-manometer catheter 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 the lung tissue of the HFD group was decreased, and the 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 ND group. CONCLUSIONS: The results suggest that metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced PH during reoxygenation.
Authors: Alagarraju Muthukumar; Madhusudhanan Narasimhan; Quan-Zhen Li; Lenin Mahimainathan; Imran Hitto; Franklin Fuda; Kiran Batra; Xuan Jiang; Chengsong Zhu; John Schoggins; James B Cutrell; Carol L Croft; Amit Khera; Mark H Drazner; Justin L Grodin; Benjamin M Greenberg; Pradeep P A Mammen; Sean J Morrison; James A de Lemos Journal: Circulation Date: 2021-06-16 Impact factor: 29.690