Screening for Myocardial Infarction Biomarkers Using Plasma Proteomics:a Mendelian Randomization Study With Validation in Animal Models and Human Populations
10.3969/j.issn.1000-3614.2025.11.003
- VernacularTitle:基于血浆蛋白质组学筛选心肌梗死生物标志物——一项孟德尔随机化研究及动物与人群表达验证
- Author:
Xing ZHANG
1
;
Chang LIU
;
Qian XIE
;
Binbin FANG
;
Chongyang ZHANG
;
Long ZHAO
;
Yining YANG
;
Xiaomei LI
;
Xianpei WANG
Author Information
1. 新疆医科大学第一附属医院 起搏电生理科,乌鲁木齐 830054
- Publication Type:Journal Article
- Keywords:
myocardial infarction;
proteomics;
Mendelian randomization;
proteasome activator subunit 1;
vacuolar protein sorting 29
- From:
Chinese Circulation Journal
2025;40(11):1066-1075
- CountryChina
- Language:Chinese
-
Abstract:
Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.
