Xiaolei Lai1, Ying Zhang2, Mengjie Li3, Juju Shang1, Weihong Liu3, Mingxue Zhou3, Hongxu Liu1. 1. Department of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. 2. Department of TCM, Beijing Luhe Hospital, Capital Medical University. 3. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing, China.
Abstract
BACKGROUND: Moderate autophagy plays a positive role in the prevention of atherosclerosis. Aberrant promoter methylation of autophagic genes can affect autophagy. Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, can prevent atherosclerosis in high-fat-fed mice. However, its precise mechanism remains unclear. This study investigated the mechanism of SYDC in ameliorating atherosclerosis in a mice model. METHODS: After 6 weeks of a high-fat diet, apolipoprotein E knockout (apoE-/-) mice were randomly grouped into control, Lipitor, and SYDC groups (n = 10). The mice were intragastrically administered with the respective drugs for 6 weeks. The expressions of Beclin1 and Atg5-Atg12 complex in atherosclerotic plaques of the mice were measured. The levels of 5-mC and DNA methyltransferase 1 (DNMT1) in the plasma of the mice were determined. The average methylation rate of CpG islands in the promoter region of autophagy-related protein (Atg13) and the mRNA expression of Atg13 in the aortas of the mice were determined. RESULTS: SYDC up-regulated the expressions of Atg5-Atg12 complex and Beclin-1 in atherosclerotic plaques (p < 0.01). Moreover, SYDC decreased the 5-mC and DNMT1 levels in plasma and atherosclerotic plaques of the mice (p < 0.01), and also decreased the average methylation rate of CpG islands in the promoter region of Atg13 and increased the mRNA levels of Atg13 in the aortas of atherosclerotic mice (p < 0.01). CONCLUSIONS: SYDC attenuates atherosclerosis by promoting autophagy, probably through regulating genomic DNA methylation and Atg13 promoter demethylation.
BACKGROUND: Moderate autophagy plays a positive role in the prevention of atherosclerosis. Aberrant promoter methylation of autophagic genes can affect autophagy. Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, can prevent atherosclerosis in high-fat-fed mice. However, its precise mechanism remains unclear. This study investigated the mechanism of SYDC in ameliorating atherosclerosis in a mice model. METHODS: After 6 weeks of a high-fat diet, apolipoprotein E knockout (apoE-/-) mice were randomly grouped into control, Lipitor, and SYDC groups (n = 10). The mice were intragastrically administered with the respective drugs for 6 weeks. The expressions of Beclin1 and Atg5-Atg12 complex in atherosclerotic plaques of the mice were measured. The levels of 5-mC and DNA methyltransferase 1 (DNMT1) in the plasma of the mice were determined. The average methylation rate of CpG islands in the promoter region of autophagy-related protein (Atg13) and the mRNA expression of Atg13 in the aortas of the mice were determined. RESULTS: SYDC up-regulated the expressions of Atg5-Atg12 complex and Beclin-1 in atherosclerotic plaques (p < 0.01). Moreover, SYDC decreased the 5-mC and DNMT1 levels in plasma and atherosclerotic plaques of the mice (p < 0.01), and also decreased the average methylation rate of CpG islands in the promoter region of Atg13 and increased the mRNA levels of Atg13 in the aortas of atherosclerotic mice (p < 0.01). CONCLUSIONS: SYDC attenuates atherosclerosis by promoting autophagy, probably through regulating genomic DNA methylation and Atg13 promoter demethylation.
Entities:
Keywords:
Atg13; Atherosclerosis; Autophagy; DNA methylation; Shen-Yuan-Dan Capsule
Authors: Babak Razani; Chu Feng; Trey Coleman; Roy Emanuel; Haitao Wen; Seungmin Hwang; Jenny P Ting; Herbert W Virgin; Michael B Kastan; Clay F Semenkovich Journal: Cell Metab Date: 2012-03-20 Impact factor: 27.287
Authors: Peter D Gluckman; Mark A Hanson; Tatjana Buklijas; Felicia M Low; Alan S Beedle Journal: Nat Rev Endocrinol Date: 2009-06-02 Impact factor: 43.330
Authors: H Robert Superko; Robert Roberts; Arthur Agatston; Stephen Frohwein; Jason S Reingold; Thomas J White; John J Sninsky; Basil Margolis; Kathryn M Momary; Brenda C Garrett; Spencer B King Journal: Curr Atheroscler Rep Date: 2011-10 Impact factor: 5.113
Authors: Xiao Rong Yang; Elaine Wat; Yan Ping Wang; Chun Hay Ko; Chi Man Koon; Wing Sum Siu; Si Gao; David Wing Shing Cheung; Clara Bik San Lau; Chuang Xing Ye; Ping Chung Leung Journal: Evid Based Complement Alternat Med Date: 2013-07-09 Impact factor: 2.629