Acrolein-induced atherosclerosis via AMPK/SIRT1-CLOCK/BMAL1 pathway and the protection from intermittent fasting
Qianfeng Chen1
Yuxia Zhong2
Bohan Li2
Yucong Feng2
Yuandie Zhang2
Tao Wei2
Margaret Zaitoun2
Shuang Rong3
Hua Wan4
Qing Feng2
1.Department of Nutrition and Food Hygiene,Key Laboratory of Toxicology,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Nosocomial Infection Management,Suzhou Wujiang District Children's Hospital,Suzhou,Jiangsu 215299,China2.Department of Nutrition and Food Hygiene,Key Laboratory of Toxicology,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China3.Department of Preventive Medicine,Department of Nutritional Health and Toxicology,School of Public Health,Wuhan University of Science and Technology,Wuhan,Hubei 430065,China4.Healthcare Center,Sir Run Run Hospital,Nanjing Medical University,Nanjing,Jiangsu 211112,China
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 ApoE-/-mice.Upon exposure to acrolein,the expression of RelA,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,short-term 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.
机标关键词：protectionpathwaybmal1ampkfromacroleinatherosclerosisfasting
分类号：R543(心脏、血管（循环系）疾病)
论文发表日期：2025-11-30
在线出版日期：2026-01-15（本平台首次上网日期，不代表文献的发表时间）
页数：16( 549-563,中插1-中插2 )
英文信息