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Updated: Jan 16, 2026
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Plasma Proteome Analysis Identifies Vascular Endothelial Growth Factor Receptor 1 as a Prognostic Biomarker in
Christian Jung1,2, Alexander Lang1, Dragos Duse1
1Department of Cardiology, Pulmonology and Vascular Medicine, University Hospital and Medical Faculty, Heinrich-Heine University, Germany. (C.J., A.L., D.A.D., R.R.B., G.W., E.Z., S.P., M.K., N.G.).
Insights
Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) is a novel biomarker for cardiogenic shock (CS) following acute myocardial infarction (AMI). Elevated VEGFR1 levels indicate a higher risk of mortality in AMI patients with CS.
Area of Science:
- Cardiology
- Proteomics
- Biomarker Discovery
Background:
- Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI) with poor patient outcomes.
- There is an urgent need for specific biomarkers to improve therapies and prognostication in CS.
- This study aimed to identify and validate novel plasma biomarkers for CS using proteomic analysis.
Purpose of the Study:
- To identify novel plasma biomarkers for cardiogenic shock (CS) in patients with acute myocardial infarction (AMI).
- To validate the prognostic relevance of identified biomarkers for 180-day survival in a large cohort of AMICS patients.
Main Methods:
- Plasma proteomic screening was performed using proximity extension assay (Olink Explore) on 17 patients (9 without shock, 8 with CS).
- Candidate biomarkers were validated in 421 AMICS patients from the CULPRIT-SHOCK cohort.
- Prognostic relevance was assessed for 180-day survival using Cox regression analysis.
Main Results:
- Proteome profiling identified Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) as significantly elevated in AMICS patients.
- Higher VEGFR1 levels in the validation cohort were associated with increased 180-day mortality (P<0.001).
- VEGFR1 provided independent prognostic information for mortality risk, even after adjusting for clinical scores and serum lactate levels.
Conclusions:
- Plasma proteomic screening successfully identified VEGFR1 as an early biomarker in patients with AMICS.
- VEGFR1 demonstrated independent prognostic value for 180-day mortality in a large, well-defined AMICS cohort.
- VEGFR1 has the potential to improve risk stratification and patient management in cardiogenic shock.
Background:
Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI) leading to poor outcomes. Specific biomarkers, with subsequent validation of their prognostic relevance in CS, are urgently needed to improve therapies and outcomes. Accordingly, the present study investigated the plasma proteome using proximity extension assay technology to identify novel specific biomarkers with subsequent validation of their prognostic relevance in CS.
Methods:
Using proximity extension assay (Olink Explore, 2942 proteins), the proteomic signature in the plasma of 9 AMI patients without shock and 8 AMI patients with CS (AMICS; exploration cohort) at admission was analyzed. Candidate biomarkers were measured in the plasma of 421 patients with AMICS from the CULPRIT-SHOCK cohort (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock; REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549, validation cohort). Their prognostic relevance was assessed for 180-day survival as the primary end point.
Results:
Proteome profiling was successful for 2925 proteins and identified VEGFR1 (vascular endothelial growth factor receptor 1, also known as Flt1) as elevated in AMICS compared with nonshock AMI in the exploration cohort (P<0.001). In patients from the independent validation cohort, nonsurvivors had markedly higher VEGFR1 levels (6.8 versus 3.8 ng/L; P<0.001). In Cox regression, VEGFR1 levels were independently associated with a higher 180-day mortality risk even after adjusting for the Simplified Acute Physiology Score II (per ng/L; adjusted hazard ratio, 1.06 [95% CI, 1.03-1.09]; P<0.001) and yielded incremental prognostic information in addition to serum lactate levels (P<0.001). The levels of VEGFR1 in surviving (30 days; n=29) and nonsurviving (n=21) patients with AMICS were determined at different time points (days 0, 1, and 5) in a third cohort, showing continuously higher levels in nonsurvivors.
Conclusions:
Plasma proteomic screening identified VEGFR1 as an early biomarker in patients with AMICS that provided independent prognostic information in a large cohort of well-defined patients with AMICS.
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