Naoxintong capsules modulates tumor necrosis factor--induced endothelial senescence through silent information
Qianyun Guo1, Bin Zhang1, Haitong Zhang1
1State key Laboratory of Cardiovascular Disease, Department of Coronary Heart Disease Center, Fuwai Hospital, National Center of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
Objective:
To investigate the protective effects of Naoxintong capsules ( NXT)on tumor necrosis factor-α (TNF-α) -induced senescence inendothelial cells and its mechanism.
Methods:
Human umbilical vascular endothelial cells (HUVECs) were treated with TNF-α ± NXT and assessed for silent information regulator 1 (SIRT1) expression and signaling. Cells were stained with beta-galactosidase to assess the levels of cellular senescence. SIRT1 was silenced through siRNA transfection.
Results:
TNF-α treatment led to the downregulation of SIRT1, resulting in forkhead box O1 (FoxO-1) acetylation, p53 acetylation and enhanced p21 expression. Following TNF-α treatment, higher SA β-Gal activity improved. TNF-α enhanced the migration of HUVECs and increased SIRT1 expression, both of which were attenuated by NXT treatment. The downstream targets of SIRT1 including FoxO-1/p53/p21 were also modulated, and HUVECs were protected from TNF-α-induced senescence. In contrast, the NXT-mediated protection was prevented by SIRT1 silencing.
Conclusions:
These findings suggest that sustained endothelial senescence can be induced by TNF-α stimulation via the SIRT1/FoxO-1/p53/p21 pathway. The protection of NXT against TNF- was partially mediated through its effects on SIRT1. This highlights the promise of NXT as a therapeutic for atherosclerosis.
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