Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40–65: a prospective cross-sectional study

Cardiovascular Diabetology

Research

Lie-Jing Lu¹  Xiao-Qiao Wang²  Ren-Jie Cai³  Lin-Feng Sun³  Cheng-Feng Luo³  Ru-Qin Xu³  Pei Mo³  Xiao-Zhen Lin³  Wen-Chao Ou³  Chong-Yu Zhang³  Jia-Yuan Chen⁴  Yun Zhong⁴ 

[1] Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guang Zhou, China;Department of Anesthesiology, the Second Affiliated Hospital of Guangzhou Medical University, Guang Zhou, China;Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guang Zhou, China;Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guang Zhou, China;No.250 Changgang Road, Guangzhou, Haizhu district, China;

关键词: Metabolomics;    Obese;    Coronary artery disease;    Hyperhomocysteinemia;    S-adenosylhomocysteine;    Cohort;    ROC analysis;   

DOI  :  10.1186/s12933-023-01942-0

 received in 2023-05-15, accepted in 2023-07-26,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundClinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD.MethodsSixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model.ResultsWe found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2–2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables.ConclusionThis is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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