Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.
Clin Interv Aging. 2021 Mar 15;16:465-474. doi: 10.2147/CIA.S298743. eCollection 2021.
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.
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.
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, < 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.
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.
氨基酸在蛋白质构建和代谢中发挥着重要作用。我们的研究旨在提供早发性冠状动脉疾病（EOCAD）患者血清中氨基酸变化的特征，并鉴定潜在的疾病生物标志物。
采用超高效液相色谱-多重反应监测-多级/质谱（UPLC-MRM-MS/MS）法测定EOCAD 患者样本池中的氨基酸谱。在验证阶段，测定每个样本中感兴趣的候选氨基酸的血清水平。
共纳入 128 例 EOCAD 患者和 64 例健康对照者。鉴定出 8 种与疾病状态相关的血清氨基酸。与对照组相比，患者组血清中 7 种氨基酸（精氨酸、蛋氨酸、酪氨酸、丝氨酸、天冬氨酸、苯丙氨酸和谷氨酸）水平升高，1 种氨基酸（4-羟脯氨酸）水平降低。验证阶段的结果表明，心肌梗死（MI）患者血清 4-羟脯氨酸水平（9.889 ± 3.635 μg/mL）明显低于对照组（16.433 ± 4.562 μmol/L， < 0.001）。升高的血清 4-羟脯氨酸水平是 MI 的独立保护因素（OR=0.863，95%CI：0.822-0.901）。MI 患者血清 4-羟脯氨酸水平与心肌肌钙蛋白 I 呈显著负相关（r=-0.667）。
我们提供了 EOCAD 患者的血清氨基酸谱，并筛选出 8 种与疾病状态相关的氨基酸，还表明 4-羟脯氨酸是早期 MI 进一步生物标志物研究的有前途的靶标。
