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: Haifeng Jin, Yueyue Wang, Lei Zhou, Lu Liu, Peng Zhang, Wuguo Deng, Yuhui Yuan
• Journal: Journal of pineal research (J Pineal Res) Vol. 57 Issue 4 Pg. 442-50 (Nov 2014) ISSN: 1600-079X [Electronic] England
• PMID: 25251287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Melatonin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Blotting, Western
• Cell Proliferation (drug effects)
• Hypertension, Pulmonary (etiology, physiopathology)
• Hypoxia (complications)
• Immunohistochemistry
• Inflammation (etiology)
• Male
• Melatonin (pharmacology)
• Myocytes, Smooth Muscle (drug effects)
• Pulmonary Artery (drug effects)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction