Sclerostin aggravates cardiac remodeling after myocardial infarction by inhibition of Wnt/β-catenin signaling pathway.

Background: The serum levels of sclerostin (SOST) are significant elevated in patients with pathological cardiac remodeling after myocardial infarction (MI). However, the mechanisms of SOST in cardiac remodeling remain largely uncharacterized. Methods: Collecting patients with MI who presented with or without left ventricular (LV) remodeling, we investigated differences in SOST expression. The influence of overexpression and silenced of SOST on the angiogenesis of cardiac microvascular endothelial cells (CMECs) was explored through Results: Serum SOST was significantly increased in patients with cardiac remodeling. Increased SOST expression was also observed in the infarcted hearts of C57BL/6 mice that underwent ligation of the left anterior descending branch of the coronary artery to induce MI. Furthermore, loss and gain of function experiments were conducted to investigate the role of SOST in post-infarct cardiac remodeling Conclusions: The present study demonstrated that SOST aggravates post-infarct pathological myocardial remodeling by inhibiting angiogenesis of CMECs while promoting the proliferation of CFs, and this may be mediated by the Wnt signaling pathway. These results suggested that SOST might act as a biomarker to predict detrimental postinfarct cardiac remodeling, and may be a potential therapeutic target for the treatment of MI.