Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis

Circ Heart Fail. 2013 Jan;6(1):107-17. doi: 10.1161/CIRCHEARTFAILURE.112.971168. Epub 2012 Dec 10.


Background: Galectin-3 has been implicated in the development of organ fibrosis. It is unknown whether it is a relevant therapeutic target in cardiac remodeling and heart failure.

Methods and results: Galectin-3 knock-out and wild-type mice were subjected to angiotensin II infusion (2.5 µg/kg for 14 days) or transverse aortic constriction for 28 days to provoke cardiac remodeling. The efficacy of the galectin-3 inhibitor N-acetyllactosamine was evaluated in TGR(mREN2)27 (REN2) rats and in wild-type mice with the aim of reversing established cardiac remodeling after transverse aortic constriction. In wild-type mice, angiotensin II and transverse aortic constriction perturbations caused left-ventricular (LV) hypertrophy, decreased fractional shortening, and increased LV end-diastolic pressure and fibrosis (P<0.05 versus control wild type). Galectin-3 knock-out mice also developed LV hypertrophy but without LV dysfunction and fibrosis (P=NS). In REN2 rats, pharmacological inhibition of galectin-3 attenuated LV dysfunction and fibrosis. To elucidate the beneficial effects of galectin-3 inhibition on myocardial fibrogenesis, cultured fibroblasts were treated with galectin-3 in the absence or presence of galectin-3 inhibitor. Inhibition of galectin-3 was associated with a downregulation in collagen production (collagen I and III), collagen processing, cleavage, cross-linking, and deposition. Similar results were observed in REN2 rats. Inhibition of galectin-3 also attenuated the progression of cardiac remodeling in a long-term transverse aortic constriction mouse model.

Conclusions: Genetic disruption and pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development. Drugs binding to galectin-3 may be potential therapeutic candidates for the prevention or reversal of heart failure with extensive fibrosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Sugars / therapeutic use*
  • Animals
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / genetics
  • Cardiomyopathies / physiopathology
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • DNA / genetics*
  • Disease Models, Animal
  • Fibrosis / genetics
  • Fibrosis / metabolism
  • Fibrosis / prevention & control
  • Galectin 3 / antagonists & inhibitors
  • Galectin 3 / biosynthesis
  • Galectin 3 / genetics*
  • Gene Expression*
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Heart Failure / prevention & control*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Knockout
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ventricular Remodeling*


  • Amino Sugars
  • Collagen Type I
  • Galectin 3
  • N-acetyllactosamine
  • DNA