title: Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis.
abstract: The present study aimed to confirm whether the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) is a sensitive indicator, and whether it can be used as a biomarker for the clinical diagnosis of atherosclerosis. Apolipoprotein E (ApoE)-/- mice were randomly divided into four groups and fed with a high methionine diet for 15 weeks. Serum levels of homocysteine (Hcy) were measured using an automatic biochemistry analyzer. The concentrations of SAM and SAH were determined using high‑performance liquid chromatography. The methylation levels of B1 repetitive elements, adipocyte fatty acid binding protein (FABP4), monocyte chemoattractant protein-1 (MCP-1) and extracellular superoxide dismutase (EC‑SOD) were analyzed using nested touchdown-methylation-specific-polymerase chain reaction analysis. After 15 weeks, compared with the normal control group, serum concentrations of Hcy were significantly increased by 1.15‑, 2.54‑ and 1.17‑fold (P<0.05) in the ApoE‑/‑ control group, Meth group and Meth‑F group, respectively. The sizes of the atherosclerotic lesions were increased in the ApoE‑/‑ control group, Meth group and Meth‑F group, by up to 1.44‑, 2.40‑ and 1.45‑fold, respectively, compared with the normal control group (P<0.05). The concentrations of SAM were significantly increased by 3.02‑, 3.42‑ and 2.46‑fold in the ApoE‑/‑ control group, Meth group and Meth‑F group, respectively (P<0.05). The ratios of SAM/SAH were increased by 1.67‑ and 2.75‑fold in the in ApoE‑/‑ control group and Meth group, respectively, compared with the normal control group. The methylation levels of B1 repetitive elements, FABP4, MCP‑1 and EC‑SOD were decreased and exhibited hypomethylation. The methylation statuses of these genes were correlated with the ratio of the serum levels of SAM and SAH. These findings suggested that the SAM/SAH ratio is a biomarker and may provide a sensitive indicator for the clinical diagnosis of atherosclerosis.
authors.affiliation: Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Public Health, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Shengchao
authors.initials: S
authors.lastname: Ma
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Fanqi
authors.initials: F
authors.lastname: Kong
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Anning
authors.initials: A
authors.lastname: Yang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Jue
authors.initials: J
authors.lastname: Tian
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Yideng
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Public Health, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D018932:Chemokine CCL2 / Q000235:genetics; D019175:DNA Methylation; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D020071:Interspersed Repetitive Sequences; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000097:blood / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D018932:Chemokine CCL2; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase