Document Detail

Deep Proteome Profiling of Circulating Granulocytes Reveals Bactericidal/Permeability-Increasing Protein as a Biomarker for Severe Atherosclerotic Coronary Stenosis.
MedLine Citation:
PMID:  23020738     Owner:  NLM     Status:  Publisher    
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 last 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 (CTO) and matched control patients using stable isotope peptide labeling, two-dimensional LC-MS/MS and data-dependent decision tree fragmentation. Over 3,000 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 CTO patients 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.
Onno B Bleijerveld; Patrick Wijten; Salvatore Cappadona; Elizabeth A McClellan; Ayse Nur Polat; Reinout Raijmakers; Jan-Willem Sels; Loes Colle; Simona Grasso; Henk W P van den Toorn; Bas van Breukelen; Andrew Stubbs; Gerard Pasterkamp; Albert J R Heck; Imo E Hoefer; Arjen Scholten
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-1
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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