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Updated: May 18, 2026
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
Deep proteome profiling of circulating granulocytes reveals bactericidal/permeability-increasing protein as a
Onno B Bleijerveld1, Patrick Wijten, Salvatore Cappadona
1Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University and Netherlands Proteomics Centre, Utrecht, The Netherlands.
Insights
Researchers identified a new biomarker for severe coronary artery disease. Bactericidal/permeability-increasing protein (BPI) was found to be down-regulated in patients with coronary occlusion, suggesting its potential for risk identification.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Immunology
Background:
- Coronary atherosclerosis is a leading cause of death, often progressing asymptomatically.
- Identifying patients at risk requires novel biomarkers due to the disease's insidious nature.
- Innate immune system involvement in vascular disease suggests potential leukocyte-based biomarkers.
Purpose of the Study:
- To discover biomarkers for severe atherosclerotic coronary stenosis using proteomics.
- To investigate the proteome of circulating leukocytes in patients with coronary artery disease.
Main Methods:
- Quantitative proteomics (stable isotope labeling, 2D LC-MS/MS) was used on granulocytes from coronary occlusion patients and controls.
- Candidate biomarkers were filtered and validated using label-free LC-MS/MS in discovery and independent cohorts.
- Proteomic profiling identified over 3000 proteins, with 57 candidates meeting stringent criteria.
Main Results:
- Bactericidal/permeability-increasing protein (BPI) was identified as a promising biomarker candidate.
- BPI levels were significantly down-regulated in circulating granulocytes of patients with chronic total coronary occlusion (CTO).
- The study successfully identified and verified potential biomarkers for severe coronary stenosis.
Conclusions:
- Bactericidal/permeability-increasing protein (BPI) shows potential as a biomarker for severe atherosclerotic coronary stenosis.
- Down-regulation of BPI in granulocytes may indicate advanced disease and could aid in patient risk stratification.
- Proteomic analysis of leukocytes offers a viable strategy for discovering novel cardiovascular disease biomarkers.
Abstract:
Coronary atherosclerosis represents the major cause of death in Western societies. As atherosclerosis typically progresses over years without giving rise to clinical symptoms, biomarkers are urgently needed to identify patients at risk. Over the past decade, evidence has accumulated suggesting cross-talk between the diseased vasculature and cells of the innate immune system. We therefore employed proteomics to search for biomarkers associated with severe atherosclerotic coronary lumen stenosis in circulating leukocytes. In a two-phase approach, we first performed in-depth quantitative profiling of the granulocyte proteome on a small pooled cohort of patients suffering from chronic (sub)total coronary occlusion and matched control patients using stable isotope peptide labeling, two-dimensional LC-MS/MS and data-dependent decision tree fragmentation. Over 3000 proteins were quantified, among which 57 candidate biomarker proteins remained after stringent filtering. The most promising biomarker candidates were subsequently verified in the individual samples of the discovery cohort using label-free, single-run LC-MS/MS analysis, as well as in an independent verification cohort of 25 patients with total coronary occlusion (CTO) and 19 matched controls. Our data reveal bactericidal/permeability-increasing protein (BPI) as a promising biomarker for severe atherosclerotic coronary stenosis, being down-regulated in circulating granulocytes of CTO patients.
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