Reduction of Activin Receptor-Like Kinase 4 Expression Ameliorates Myocardial Ischemia/Reperfusion Injury through Inhibiting TGF Signaling Pathway.

The activation of activin receptor-like kinase 4 (ALK4) signaling plays a pivotal role in the pressure-overloaded heart, and haplodeficiency of ALK4 can alleviate cardiac fibrosis secondary to myocardial infarction and preserve cardiac function through partially inactivating the Smad3/4 pathway. However, whether transforming growth factor (TGF) signaling is involved in the beneficial effects of ALK4 knockdown on the ischemic heart is still unclear. This study was undertaken to investigate the change in the TGF signaling after ALK4 knockdown and in vitro. Forty C57BL/6J mice were randomized into ALK4 ischemia/reperfusion (I/R) group (ALK4+I/R, = 10), ALK4 sham group (ALK4+sham, = 10), wild-type sham group (WT+sham, = 10), and WT I/R group (WT+I/R, = 10). Heart histology and the levels of cytokines related to antioxidant and inflammation, as well as protein and mRNA expressions of molecules associated with TGF pathway, were examined in different groups. Our results showed that the reduction of ALK4 expression ameliorated myocardial I/R injury through inhibiting TGF signaling pathway. Our findings indicate that ALK4 may become a novel target for the therapy of myocardial I/R injury.