Abstract | BACKGROUND: METHODS:
Apolipoprotein E-deficient ( apoE-/-) mice received dietary supplementation with the SAH hydrolase (SAHH) inhibitor adenosine dialdehyde or were intravenously injected with a retrovirus expressing SAHH shRNA. These 2 approaches, along with the heterozygous SAHH gene knockout ( SAHH+/-) mouse model, were used to elevate plasma SAH levels and to examine the role of SAH in aortic endothelial dysfunction. The relationship between plasma SAH levels and endothelial dysfunction was also investigated in human patients with coronary artery disease and healthy control subjects. RESULTS: CONCLUSIONS: Our findings indicate that inhibition of SAHH results in elevated plasma SAH levels and induces endothelial dysfunction via epigenetic upregulation of the p66shc-mediated oxidative stress pathway. Our study provides novel molecular insight into mechanisms of SAH-associated endothelial injury that may contribute to the development of atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03345927.
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Authors | Yunjun Xiao, Junjie Xia, Jinquan Cheng, Haiyan Huang, Yani Zhou, Xifei Yang, Xuefen Su, Yuebin Ke, Wenhua Ling |
Journal | Circulation
(Circulation)
Vol. 139
Issue 19
Pg. 2260-2277
(05 07 2019)
ISSN: 1524-4539 [Electronic] United States |
PMID | 30773021
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Small Interfering
- Shc1 protein, mouse
- Src Homology 2 Domain-Containing, Transforming Protein 1
- periodate-oxidized adenosine
- S-Adenosylhomocysteine
- Adenosylhomocysteinase
- Adenosine
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Topics |
- Adenosine
(administration & dosage, analogs & derivatives, pharmacology)
- Adenosylhomocysteinase
(antagonists & inhibitors, genetics, metabolism)
- Aged
- Animals
- Atherosclerosis
(metabolism)
- Coronary Artery Disease
(metabolism)
- DNA Methylation
- Disease Models, Animal
- Endothelium, Vascular
(physiology)
- Epigenesis, Genetic
- Female
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout, ApoE
- Middle Aged
- Oxidative Stress
- RNA, Small Interfering
(genetics)
- S-Adenosylhomocysteine
(blood)
- Signal Transduction
- Src Homology 2 Domain-Containing, Transforming Protein 1
(genetics, metabolism)
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