期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 958, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2023.176071
关键词
SOX4; Pathological cardiac hypertrophy; SIRT3
Pathological cardiac hypertrophy can be reduced by decreasing the expression of SOX4, which regulates SIRT3 expression and affects the levels of ROS and oxidative stress in the heart.
Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II) treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.
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