Upregulated galectin-3 is not a critical disease mediator of cardiomyopathy induced by β2-adrenoceptor overexpression.

Preclinical studies have demonstrated that anti-galectin-3 (Gal-3) interventions are effective in attenuating cardiac remodeling, fibrosis, and dysfunction. We determined, in a transgenic (TG) mouse model of fibrotic cardiomyopathy, whether Gal-3 expression was elevated and whether Gal-3 played a critical role in disease development. We studied mice with fibrotic cardiomyopathy attributable to cardiac overexpression of human β₂-adrenoceptors (β₂-TG). Cardiac expression levels of Gal-3 and fibrotic or inflammatory genes were determined. The effect of Gal-3 inhibition in β₂-TG mice was studied by treatment with Gal-3 inhibitors (N-acetyllactosamine and modified citrus pectin) or by deletion of Gal-3 through crossing β₂-TG and Gal-3 knockout mice. Changes in cardiomyopathy phenotypes were assessed by echocardiography and biochemical assays. In β₂-TG mice at 3, 6, and 9 mo of age, upregulation of Gal-3 expression was observed at mRNA (~6- to 15-fold) and protein (~4- to 8-fold) levels. Treatment of β₂-TG mice with N-acetyllactosamine (3 wk) or modified citrus pectin (3 mo) did not reverse cardiac fibrosis, inflammation, and cardiomyopathy. Similarly, Gal-3 gene deletion in β₂-TG mice aged 3 and 9 mo did not rescue the cardiomyopathy phenotype. In conclusion, the β₂-TG model of cardiomyopathy showed a robust upregulation of Gal-3 that correlated with disease severity, but Gal-3 inhibitors or Gal-3 gene deletion had no effect in halting myocardial fibrosis, remodeling, and dysfunction. Gal-3 may not be critical for cardiac fibrogenesis and remodeling in this cardiomyopathy model. [ABSTRACT FROM AUTHOR]