Tissue taurine depletion induces profibrotic pattern of gene expression and causes aging-related cardiac fibrosis in heart in mice

Abstract

Dietary taurine deficiency results in dilated cardiomyopathy in cats while in mice taurine deficiency produced by knocking out the taurine transporter (TauT) gene leads to a reduction in cardiac function with advancing age. The present study elucidated the involvement of cardiac fibrosis in the aging-dependent cardiac disorder of the TauT-knockout (TauTKO) mouse. Old (18-4-month-old) TauTKO mice, but not young (3-month-old) mice, exhibit cardiac fibrosis. Transcriptome microarray analysis revealed an increase in pro-fibrotic genes, such as S100A4, ACTA2 and CTGF, in both young and old TauTKO hearts. Based on transcriptome-pathway analysis the genes involved in "organization of extracellular matrix, such as LGALS3, are enriched in old TauTKO hearts compared to old wild-type hearts, suggesting the contribution of these genes to fibrosis. In conclusion, taurine depletion predisposes the heart to fibrosis, which leads to cardiac fibrosis upon aging.