Inhibition of Transverse Aortic Constriction Induced Myocardial Hypertrophy by Knocking out the Target of the Early Growth Response-1 to Inhibit Apoptosis and Autophagy

Abstract

Myocardial hypertrophy, a significant contributor to the development of heart failure, continues to be prevalent. Early growth response-1 (EGR-1) is closely linked to the development of diverse myocardial conditions. The target of EGR1 (TOE1) is a critical factor in myocardial hypertrophy, but its regulatory function remains unclear. Myocardial cell injury was induced by angiotensin II. TOE1 knockout mice and cells were generated to investigate its impact on myocardial hypertrophy. TUNEL staining was employed to assess cell apoptosis. Furthermore, western blotting and qRT-PCR were performed to measure the expression of target genes. The results revealed that knockout of TOE1 effectively inhibited myocardial hypertrophy and injury caused by transverse aortic constriction. In vivo experiments demonstrated that TOE1 knockout improved myocardial function and suppressed inflammatory factors, oxidative stress, apoptosis, and autophagy levels. In vitro, TOE1 knockout suppressed cell apoptosis, mitochondrial damage, and the intensity of reactive oxygen species. Additionally, it inhibited the expression of apoptosis- and autophagy-related genes. These findings introduce a promising avenue for preventing and treating myocardial hypertrophy.