摘要
The circadian clock is crucial for the progression of cardiovascular diseases.Our previous studies showed that acrolein,an environmental pollutant,exacerbated atherosclerosis by reducing CLOCK/BMAL1 levels and disrupting circadian rhythm;in contrast,intermittent fasting(IF),a dietary regimen,ameliorated acrolein-induced atherosclerosis.In the current study,mice were administered acrolein at a dose of 3 mg/(kg·day)via drinking water and subjected to IF for 18 h(from 0:00 to 18:00).We observed that IF reduced the formation of aortic lesions accelerated by acrolein in Apo E-/-mice.Upon exposure to acrolein,the expression of Rel A,Il1b,and Tnf increased in the liver and heart tissues,but these changes were reversed by IF treatment.Notably,IF treatment upregulated the expression of adenosine monophosphate(AMP)-activated protein kinase catalytic subunit alpha-1(AMPKα1),p-AMPKα1,and sirtuin 1(SIRT1),while inhibiting acrolein-induced mitogen-activated protein kinase(MAPK)activation.Additionally,the expression of circadian genes Clock/Bmal1 was suppressed and disrupted by acrolein,whereas IF restored their expression.Moreover,consistent with the in vivo findings,shortterm starvation in vitro,as a fasting cell model,alleviated the dysregulation of CLOCK/BMAL1 and upregulated SIRT1 expression by modulating the AMPK and reactive oxygen species(ROS)-MAPK pathways activated by acrolein.In summary,we demonstrated that IF suppressed the ROS-MAPK pathway but activated the AMPK pathway to enhance the expression of circadian clock genes,thereby ameliorating acrolein-induced atherogenesis,which may shed light on strategies for preventing cardiovascular diseases.
基金
supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the Key Project of Jiangsu Commission of Health(Grant No.ZD2022012)。
