Quantitative Assessment of Serum Amino Acids and Association with Early-Onset Coronary Artery Disease

Abstract

Chao Xuan,1 Hui Li,1 Qing-Wu Tian,1 Jun-Jie Guo,2 Guo-Wei He,3,4 Li-Min Lun,1 Qing Wang1 1Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Center for Basic Medical Research & Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of China; 4Department of Surgery, Oregon Health and Science University, Portland, OR, USACorrespondence: Chao XuanDepartment of Clinical Laboratory, The Affiliated Hospital of Qingdao University, No. 1677, Wutai Mountain Road, Qingdao (West Coast), 266500, People’s Republic of ChinaTel [phone]Email [email protected] WangDepartment of Clinical Laboratory, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266100, People’s Republic of ChinaTel [phone]Email [email protected]: Amino acids play essential roles in protein construction and metabolism. Our study aims to provide a profile of amino acid changes in the serum of patients with early-onset coronary artery disease (EOCAD) and identify potential disease biomarkers.Methods: Ultra-performance liquid chromatography-multiple reaction monitoring-multistage/mass spectrometry (UPLC-MRM-MS/MS) was used to determine the amino acid profile of patients with EOCAD in sample pools. In the validation stage, the serum levels of candidate amino acids of interest are determined for each sample.Results: A total of 128 EOCAD patients and 64 healthy controls were included in the study. Eight serum amino acids associated with disease state were identified. Compared with the control group, serum levels of seven amino acids (L-Arginine, L-Methionine, L-Tyrosine, L-Serine, L-Aspartic acid, L-Phenylalanine, and L-Glutamic acid) increased and one (4-Hydroxyproline) decreased in the patient group. Results from the validation stage demonstrate that serum levels of 4-Hydroxyproline were significantly lower in myocardial infarction (MI) patients (9.889 ± 3.635 μg/mL) than those in the controls (16.433 ± 4.562 μmol/L, p < 0.001). Elevated serum 4-Hydroxyproline levels were shown to be an independent protective factor for MI (OR = 0.863, 95% CI: 0.822– 0.901). The significant negative correlation was seen between serum 4-Hydroxyproline levels and cardiac troponin I (r = − 0.667) in MI patients.Conclusion: We have provided a serum amino acid profile for EOCAD patients and screened eight disease state-related amino acids, and we have also shown that 4-Hydroxyproline is a promising target for further biomarker studies in early-onset MI.Keywords: amino acid, coronary artery disease, myocardial infarction, 4-Hydroxyproline

Keywords

• amino acid
• coronary artery disease
• myocardial infarction
• 4-hydroxyproline.