Deep plasma proteomic analysis of patients with left ventricular remodeling after a first myocardial infarction

Abstract

Depletion of major blood proteins is one of the most promising approaches to accessing low abundance biomarkers for proteomics studies. The use of combinatorial peptide ligand library (CPLL) for accessing these low abundance proteins in plasma from patients with a myocardial infarction (MI) was tested to identify candidate protein biomarkers of left ventricular remodeling (LVR). Serial blood samples of MI patients followed for one year (at inclusion, 1 month, 3 months, and 1 year) were treated with CPLL and analyzed by SELDI-TOF-MS. The use of CPLL increased resolution, with loss of most abundant plasma proteins, reproducibly and improved the intensity of low-abundance proteins. Longitudinal information allowed us to reduce by 55% the final number of peaks identified as significantly modulated throughout the 1-year follow-up after MI. Interestingly, 19 of the 26 peaks finally selected were detected only in samples treated from CPLL. The 2777 m/z peak, found in less elevated level in high remodeling patients, was identified as being DAHKSEVAHR FKDLGEENFKALVL, the N-terminal peptide (24-48 aa) generated from albumin by pepsin cleavage. This finding shows the potential of CPLL in accessing low-abundance proteins to select and identify candidate biomarkers in patients with LVR.