Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice

Hypertension. 2016 Mar;67(3):606-12. doi: 10.1161/HYPERTENSIONAHA.115.06161. Epub 2016 Jan 18.


Galectin-3 (Gal-3) is involved in inflammation, fibrogenesis, and cardiac remodeling. Previous evidence shows that Gal-3 interacts with aldosterone in promoting macrophage infiltration and vascular fibrosis and that Gal-3 genetic and pharmacological inhibition prevents remodeling in a pressure-overload animal model of heart failure. We aimed to explore the contribution of Gal-3 and aldosterone in mechanisms leading to heart failure in a murine model. Male mice with cardiac-specific hyperaldosteronism underwent isoproterenol subcutaneous injections, to be then randomized to receive placebo, a Gal-3 inhibitor (modified citrus pectin [MCP]), an aldosterone antagonist (potassium canrenoate), or MCP+canrenoate for 14 days. Isoproterenol induced a rapid and persistent decrease in left ventricular fractional shortening (-20% at day 14); this was markedly improved by treatment with either MCP or canrenoate (both P<0.001 versus placebo). MCP and canrenoate also reduced cardiac hypertrophy and fibrosis and the expression of genes involved in fibrogenesis (Coll-1 and Coll-3) and macrophage infiltration (CD-68 and MCP-1). After isoproterenol, Gal-3 gene expression (P<0.05 versus placebo) and protein levels (-61% and -69% versus placebo) were decreased by both canrenoate and MCP. The combined use of antagonists of Gal-3 and aldosterone resulted in more pronounced effects on cardiac hypertrophy, inflammation, and fibrosis, when compared with either MCP or canrenoate alone. Inhibition of Gal-3 and aldosterone can reverse isoproterenol-induced left ventricular dysfunction, by reducing myocardial inflammation and fibrogenesis. Gal-3 likely participates in mechanisms of aldosterone-mediated myocardial damage in a heart failure murine model with cardiac hyperaldosteronism. Gal-3 inhibition may represent a new promising therapeutic option in heart failure.

Keywords: aldosterone; fibrosis; galectin-3; heart; inflammation; isoproterenol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Echocardiography
  • Fibrosis
  • Galectin 3 / antagonists & inhibitors
  • Galectin 3 / biosynthesis
  • Galectin 3 / genetics*
  • Gene Expression Regulation*
  • Heart Ventricles / pathology*
  • Heart Ventricles / physiopathology
  • Isoproterenol / toxicity
  • Male
  • Mice
  • Mice, Transgenic
  • Myocardium / metabolism
  • Myocardium / pathology
  • RNA / genetics*
  • Signal Transduction
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / diagnosis
  • Ventricular Dysfunction, Left / genetics*


  • Galectin 3
  • RNA
  • Isoproterenol