Pigment epithelium-derived factor maintains tight junction stability after myocardial infarction in rats through inhibition of the Wnt/β-catenin signaling pathway.

PURPOSE:The impairment of the coronary microcirculatory barrier caused by acute myocardial infarction (AMI) is closely related to poor prognosis. Recently, pigment epithelial-derived factor (PEDF) has been proven to be a promising cardiovascular protective drug. In this study, we demonstrated the protective role of PEDF in endothelial tight junctions (TJs) and the vascular barrier in AMI. MATERIALS AND METHODS:2, 3, 5-triphenyltetrazolium chloride (TTC), echocardiography and immunofluorescence staining were used to observe the size of infarcted myocardium area and cardiac function in myocardial tissue, and the distribution of TJ proteins in human coronary endothelial cells (HCAEC). Dextran leakage assay and Transwell were used to assess the extent of vascular and HCAEC leakage. Polymerase chain reaction (PCR) and Western blot were used to detect TJ-related mRNA and protein, and signaling pathway protein expression. RESULTS:PEDF effectively reduced the infarction area and improved cardiac function in AMI rats, and lowered the leakage in AMI rats' angiocarpy and oxygen-glucose deprivation (OGD)-treated HCAEC. Furthermore, PEDF upregulated the expression of TJ mRNA and proteins in vivo and vitro. Mechanistically, PEDF inhibited the expression of phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) and active β-catenin under OGD, thus suppressing the activation of the classical Wnt pathway. CONCLUSIONS:These novel findings demonstrated that PEDF maintained the expression of TJ proteins and endothelial barrier integrity by inhibiting the classical Wnt pathway during AMI.