Galectin-3 mediates pulmonary vascular remodeling in hypoxia-induced pulmonary arterial hypertension

J Am Soc Hypertens. 2017 Oct;11(10):673-683.e3. doi: 10.1016/j.jash.2017.07.009. Epub 2017 Jul 28.


Pulmonary vascular adventitia serves as a key regulator of pulmonary vascular remodeling in the pathogenesis of pulmonary arterial hypertension (PAH). Excessive proliferation and differentiation of pulmonary adventitial fibroblasts (PAFs) are proven to be crucial in the pathogenesis of PAH. Galectin-3 (Gal-3) is known as a key fibroblasts activating factor which is involved in the fibrogenesis of several diseases, such as pulmonary fibrosis, vascular fibrosis, and heart failure. Therefore, we seek to investigate the potential role of Gal-3 in regulating PAF cells in the pathogenesis of PAH. Gal-3 plasma concentration was significantly higher in PAH patients. Gal-3 was upregulated in pulmonary artery adventitia of hypoxia-induced PAH rats. Inhibition of Gal-3 with N-Acetyl-D-lactosamine (N-Lac) ameliorated PAH and pulmonary vascular remodeling. Gal-3 can stimulate the proliferation, differentiation, and collagen synthesis of PAFs, which was reversed by N-Lac. Transforming growth factor β1 increased Gal-3 expression in PAFs, whereas N-Lac significantly suppressed transforming growth factor β1-induced proliferation, differentiation, and collagen synthesis of PAFs. Gal-3 serves as a critical regulator in the pathogenesis of PAH by regulating the proliferation, differentiation, and extracellular matrix deposition synthesis of PAFs. Inhibition of Gal-3 may represent a novel therapeutic target for PAH treatment.

Keywords: Differentiation; TGF-β1; fibrotic response; galectin-3; pulmonary arterial adventitial fibroblasts.

MeSH terms

  • Adult
  • Adventitia / cytology
  • Adventitia / pathology
  • Amino Sugars / pharmacology
  • Animals
  • Blood Proteins
  • Cell Differentiation / drug effects
  • Cell Hypoxia
  • Cell Proliferation / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Galectin 3 / blood
  • Galectin 3 / metabolism*
  • Galectins
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / pathology*
  • Lung / blood supply
  • Lung / cytology
  • Lung / pathology
  • Male
  • Middle Aged
  • Pulmonary Artery / cytology
  • Pulmonary Artery / pathology*
  • Rats
  • Transforming Growth Factor beta1 / metabolism
  • Up-Regulation
  • Vascular Remodeling*
  • Young Adult


  • Amino Sugars
  • Blood Proteins
  • Galectin 3
  • Galectins
  • LGALS3 protein, human
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • N-acetyllactosamine