Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension

Hao,Mingwen; Li,Miaomiao; Li,Wenjun

doi:10.3892/mmr.2016.6020

Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension

Authors:
- Mingwen Hao
- Miaomiao Li
- Wenjun Li
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Affiliations: Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China, Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China
Published online on: December 9, 2016 https://doi.org/10.3892/mmr.2016.6020
Pages: 160-168
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal‑3‑/‑ mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal‑3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal‑3 in wild type murine pulmonary arteries. Gal‑3 deletion reduced the hypoxia‑induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal‑3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal‑3 inhibition alleviated the hypoxia‑induced inflammatory response in HPAECs, including tumor necrosis factor‑α and interleukin‑1 secretion, expression of intercellular adhesion molecule‑1 and adhesion of THP‑1 monocytes. Gal‑3 inhibition also reduced hypoxia‑induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal‑3 inhibition suppressed HPASMC switching from a ‘contractile’ to a ‘synthetic’ phenotype. In conclusion, Gal‑3 serves a fundamental role in hypoxia‑induced PAH, and inhibition of Gal‑3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH.

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