The plasma microparticle proteome

Abstract

All cell types shed ectosomes and exosomes, collectively known as microparticles (MP; 0.1 to 1.5 μm in diameter), when activated or stressed; normal human plasma contains ~2 μg MP protein/mL. The cellular composition of plasma MP is altered in many diseases, including acute coronary syndrome, diabetes mellitus, sepsis, and sickle cell disease. We measured the plasma MP protein composition of 42 patients (median age 69.5 years, most with cardiovascular disease) by label-free liquid chromatography coupled to tandem mass spectrometry. Among 458 proteins detected with high confidence (identified by at least two unique peptides with SEQUEST XCor (Thermo Electron Corp., San Jose, CA) ≥ 2.0, 2.2, and 3.3 for charge states +1, +2, and +3, respectively), 130 were present in most patients, representing a "core" set of plasma MP proteins. This core is enriched in cytoskeletal, integrin complex, and hemostasis proteins, and spectral counts of several proteins correlate with patient age and gender. We conclude that the MP proteome may be a useful and reliable source of biologically relevant disease biomarkers.