Wnt5a is elevated in heart failure and affects cardiac fibroblast function

摘要: Wnt signaling is dysregulated in heart failure (HF) and may promote cardiac hypertrophy, fibrosis, inflammation. Blocking the ligand Wnt5a prevents HF animal models. However, role of human its functions cells remain unclear. Here, we investigated regulation patients effects on primary mouse fibroblasts. Serum was elevated associated with hemodynamic, neurohormonal, clinical measures disease severity. In failing hearts, protein correlated interleukin (IL)-6 tissue inhibitor metalloproteinase (TIMP)-1. messenger RNA (mRNA) levels were markedly upregulated myocardium both mRNA declined following left ventricular assist device therapy. fibroblasts, recombinant dose-dependently release IL-6 TIMP-1. did not affect β-catenin levels, but activated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Importantly, inhibition ERK1/2 activation attenuated Wnt5a-induced conclusion, our results show that serum progressive HF. induces TIMP-1 which might myocardial inflammation thereby contribute to progression. • upregulates (TIMP)-1 through ERK pathway. Wnt5a-mediated