Protocatechuic Aldehyde Alleviates d-Galactose-Induced Cardiomyocyte Senescence by Regulating the TCF3/ATG5 Axis

Cardiomyocyte senescence is an independent risk factor for cardiovascular diseases. Protocatechuic aldehyde (PCA) is a natural chemical in the Chinese medicinal herb Salvia miltiorrhiza. PCA could protect against oxidative stress and inflammation in the cardiovascular system. In present study, we treated H9C2 cells with d-galactose to establish an in vitro model of cardiomyocyte senescence and investigated the role and underlying mechanisms of PCA in myocardial cell senescence. It was found that d-galactose induced transcription factor 3 (TCF3) expression and decreased autophagy-related genes 5 (ATG5) expression. Meanwhile, inflammation and senescence were exacerbated by d-galactose. TCF3 transcriptionally inhibited ATG5 expression. TCF3 knockdown abolished the effects of d-galactose on H9C2 by activating ATG5-mediated autophagy. PCA hindered TCF3 and inflammation to alleviate the d-galactose-induced senescence of H9C2 cells in a dose-dependent manner. Whereas, the anti-inflammation and anti-senescence effects of PCA were reversed by TCF3 knockdown. Furthermore, absence of ATG5 partially eliminated the impacts of PCA on H9C2 cells treated with d-galactose. Conclusively, PCA alleviated d-galactose-induced senescence by downregulating TCF3, promoting ATG5-mediated autophagy, and inhibiting inflammation in H9C2 cells. These results elucidated the potential mechanism by which PCA alleviated cardiomyocyte senescence and enabled its application in treating cardiomyocyte senescence.

Automated summary

Cardiomyocyte senescence is a risk factor for cardiovascular diseases. Protocatechuic aldehyde (PCA) in Salvia miltiorrhiza protects against oxidative stress and inflammation in the cardiovascular system. This study investigates the role of PCA in myocardial cell senescence and finds that it alleviates senescence by downregulating TCF3, promoting ATG5-mediated autophagy, and inhibiting inflammation in H9C2 cells.