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Mol Med Rep. 2017 Jan;15(1):160-168. doi: 10.3892/mmr.2016.6020. Epub 2016 Dec 9.

Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension.

Author information

1
Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.
2
Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, P.R. China.

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.

PMID:
27959409
PMCID:
PMC5355711
DOI:
10.3892/mmr.2016.6020
[Indexed for MEDLINE]
Free PMC Article

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