Discovery of proteins related to coronary artery disease using industrial-scale proteomics analysis of pooled plasma

Mark P. Donahue, Keith Rose, Denis Hochstrasser, Jacky Vonderscher, Peter Grass, Salah Dine Chibout, Charlotte L. Nelson, Peter Sinnaeve, Pascal Goldschmidt, Christopher B. Granger

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background: Relating a disease state to an entire population of proteins provides an opportunity to gain new insights into a disease. Methods: Male populations of 53 patients with angiographic coronary artery disease and 53 control subjects without coronary disease from the Duke Databank for Cardiovascular Disease were established and matched for age and race as well as extremes of risk factors. Major plasma protein abnormalities were excluded. Plasma samples of each group were pooled to make large volumes (6 L each) to identify low-abundance proteins. After removal of albumin as well as immunoglobulins and enrichment of smaller proteins (<20-40 kDa), samples were separated into 12 960 fractions by cation exchange and 2 reversed-phase chromatography steps. Proteins were analyzed by liquid chromatography-electrospray ionization tandem mass spectrometry. Results: There were 731 plasma proteins or fragments identified. Of these proteins, 95 were differentially displayed in the case versus control populations. These represent broad categories of proteins involved with natural defenses, inflammation, growth, and coagulation. Conclusion: We identified a large number of proteins that differ in abundance in populations with and those without angiographic coronary disease. These proteins now comprise candidates for validation studies in individual patients and in larger clinical data sets to better define disease pathways and establish novel markers for disease.

Original languageEnglish (US)
Pages (from-to)478-485
Number of pages8
JournalAmerican Heart Journal
Volume152
Issue number3
DOIs
StatePublished - Sep 2006

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Donahue, M. P., Rose, K., Hochstrasser, D., Vonderscher, J., Grass, P., Chibout, S. D., Nelson, C. L., Sinnaeve, P., Goldschmidt, P., & Granger, C. B. (2006). Discovery of proteins related to coronary artery disease using industrial-scale proteomics analysis of pooled plasma. American Heart Journal, 152(3), 478-485. https://doi.org/10.1016/j.ahj.2006.03.007