Journal
JOURNAL OF PINEAL RESEARCH
Volume 57, Issue 4, Pages 442-450Publisher
WILEY
DOI: 10.1111/jpi.12184
Keywords
hypoxia; inflammation; melatonin; pulmonary artery smooth muscle cells; pulmonary hypertension
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Funding
- Liaoning Provence Natural Science Foundation of China [2013023043]
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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 4wk 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-1 (HIF-1), and nuclear factor-B (NF-B). 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.
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