Reduction of Activin Receptor-Like Kinase 4 Expression Ameliorates Myocardial Ischemia/Reperfusion Injury through Inhibiting TGF β 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) β 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 β signaling after ALK4 knockdown in vivo and in vitro. Forty C57BL/6J mice were randomized into ALK4 +/- ischemia/reperfusion (I/R) group (ALK4 +/- +I/R, n = 10), ALK4 +/- sham group (ALK4 +/- +sham, n = 10), wild-type sham group (WT+sham, n = 10), and WT I/R group (WT+I/R, n = 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 β pathway, were examined in different groups. Our results showed that the reduction of ALK4 expression ameliorated myocardial I/R injury through inhibiting TGF β signaling pathway. Our findings indicate that ALK4 may become a novel target for the therapy of myocardial I/R injury.