Melatonin attenuates hypoxic pulmonary hypertension by inhibiting the inflammation and the proliferation of pulmonary arterial smooth muscle cells |
| |
Authors: | Haifeng Jin Yueyue Wang Lei Zhou Lu Liu Peng Zhang Wuguo Deng Yuhui Yuan |
| |
Institution: | 1. Institute of Cancer Stem Cell, The First Affiliated Hospital, Dalian Medical University Cancer Center, , Dalian, China;2. Department of Anatomy, Qiqihar Medical University, , Qiqihar, China;3. Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, , Guangzhou, China |
| |
Abstract: | Hypoxia‐induced inflammation and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Melatonin possesses anti‐inflammatory and antiproliferative properties. However, the effect of melatonin on HPH remains unclear. In this study, adult Sprague–Dawley rats were exposed to intermittent chronic hypoxia for 4 wk to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio, and median width of pulmonary arterioles. Melatonin attenuated the elevation of RVSP, RV/LV+S, and mitigated the pulmonary vascular structure remodeling. Melatonin also suppressed the hypoxia‐induced high expression of proliferating cell nuclear antigen (PCNA), hypoxia‐inducible factor‐1α (HIF‐1α), and nuclear factor‐κB (NF‐κB). In vitro, melatonin concentration‐dependently inhibited the proliferation of PASMCs and the levels of phosphorylation of Akt and extracellular signal‐regulated kinases1/2 (ERK1/2) caused by hypoxia. These results suggested that melatonin might potentially prevent HPH via anti‐inflammatory and antiproliferative mechanisms. |
| |
Keywords: | hypoxia inflammation melatonin pulmonary artery smooth muscle cells pulmonary hypertension |
|
|