title: Melatonin attenuates hypoxic pulmonary hypertension by inhibiting the inflammation and the proliferation of pulmonary arterial smooth muscle cells.
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.
authors.affiliation: Institute of Cancer Stem Cell, The First Affiliated Hospital, Dalian Medical University Cancer Center, Dalian, China; Department of Anatomy, Qiqihar Medical University, Qiqihar, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jin
authors.forename: Yueyue
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Wuguo
authors.initials: W
authors.lastname: Deng
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008550:Melatonin
keywords: hypoxia; inflammation; melatonin; pulmonary artery smooth muscle cells; pulmonary hypertension