Abstract 2599: Proteomic Profiling of Plasma Samples in Coronary Artery Disease
Introduction: Characterization of the global protein profiles of patients with coronary artery disease has been made possible through advances in protein analytical technologies. Automated label-free relative protein quantification using mass spectrometry (LC/MS/MS) now allows the integration of global protein profiling into large clinical trials.
Methods and Results: In the present study we applied this approach to a subset of samples selected from a consecutive series of 3500 patients that underwent coronary angiography at the Heart Center. Fifty patients were randomly selected from each of five subgroups:
ST-elevation acute myocardial infarction,
non ST-elevation acute myocardial infarction,
stable angina, and
control patients without coronary artery disease.
High abundance proteins were depleted prior to tryptic digest. Tryptic peptides were analyzed using Thermo-Finnigan linear ion-trap mass spectrometer. Spectra were searched using Sequest and X! Tandem, and signal-processed at INCAPS. Peptide abundance was analyzed using the Empirical Bayes approach Limma, peptide-level quantitative information was combined into protein families using a random-effects model, and the list of differentially abundant protein families with a false discovery rate of 0.05 was determined by resampling. A total of 1949 protein families were detected and quantified. Of these, 555 protein families had at least one significant change between the groups, including 72 that have been previously associated with cardiovascular disease. The numbers of altered proteins are shown in Table 1⇓.
Conclusion: Our study provides the most comprehensive dataset of protein changes in patients with coronary artery disease described so far. We demonstrate that moderately abundant proteins may potentially be useful for risk classification in coronary artery disease.