FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt

Heart failure (HF) is the end stage of many cardiovascular diseases and seriously threatens people's health. This article aimed to explore the biological role of fat-mass and obesity-associated gene (FTO) in HF. We constructed HF mouse model by transverse aortic constriction or intraperitoneal injection of doxorubicin. Mouse myocardial cells were exposed to hypoxia/reoxygenation (H/R). FTO and Mhrt were downregulated in heart tissues of HF mice. HF mice exhibited an increase in the total levels of N-6 methyladenosine (m(6)A) and the m(6)A levels of Mhrt. Moreover, FTO overexpression caused an upregulation of Mhrt and reduced m(6)A modification of Mhrt in the H/R-treated myocardial cells. FTO upregulation repressed apoptosis of H/R-treated myocardial cells. FTO knockdown had the opposite results. Mhrt overexpression reduced apoptosis of H/R-treated myocardial cells. Moreover, the influence conferred by FTO upregulation was abolished by Mhrt knockdown. In conclusion, our data demonstrate that FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Thus, FTO may be a target gene for HF treatment.

Automated summary

The study revealed that FTO overexpression inhibits apoptosis in heart tissues of HF mice by regulating m6A modification of Mhrt, suggesting FTO as a potential target gene for HF treatment.