Transcription factor EB improves ventricular remodeling after myocardial infarction by regulating the autophagy pathway

Abstract Background Adverse left ventricular remodeling after myocardial infarction (MI) compromises cardiac function and increases heart failure risk. Till now, comprehension of the role transcription factor EB (TFEB) plays after MI is limited.ObjectivesThe purpose of this study was to describe the effects of TFEB on cell death and fibroblast differentiation after MI.MethodsAAV9 mediated up- and down-regulated TFEB expressions were generated in C57BL/6 mice two weeks before the MI modeling. Echocardiography, Masson, HE, Sirius red staining immunofluorescence, and wheat germ agglutinin staining were performed at 3 days, and 1, 2, and 4 weeks after MI modeling. Fibroblasts and myocytes collected from SD neonatal rats were transfected by adenovirus and siRNA, and cell counting kit-8 (CCK8), Cell Proliferation EdU Image (EDU), immunofluorescence, and Transwell assay were conducted. Myocardial fibrosis-related proteins and autophagy-related protein were identified by Western blot.ResultsThe up-regulation of TFEB resulted in reduced myocardial cell death, delayed fibroblasts proliferation and its differentiation into myofibroblasts, and up-regulated expression of LC3B three days after MI. Similar results were observed in vitro studies. Meanwhile, a significant up-regulation of EF, decrease in the ratio of the infarction length, and decreased protein level of collagen III were observed four weeks after MI modeling. The over-expression of TFEB slowed down myofibroblast migration and resulted in a significant down-regulation of collagen I level in myofibroblasts.ConclusionsTFEB demonstrated potential in improving cell death after MI by mediating autophagy and regulating fibroblast proliferation and transformation. Its molecular impacting mechanism deems further investigation.