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Published on: August 7, 2014
The plasma microparticle proteome
Kristina M Little1, David M Smalley, Nancy L Harthun
1Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
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.
Insights
Plasma microparticles (MPs) contain proteins that may serve as disease biomarkers. This study identified a core set of 130 proteins in human plasma MPs, offering potential for diagnostic applications.
Area of Science:
- Biochemistry
- Proteomics
- Clinical Diagnostics
Background:
- Cellular activation or stress leads to shedding of microparticles (MPs), including ectosomes and exosomes.
- Plasma MP protein composition is altered in various diseases, such as cardiovascular conditions, diabetes, sepsis, and sickle cell disease.
- Normal human plasma contains approximately 2 μg MP protein/mL.
Purpose of the Study:
- To characterize the protein composition of plasma microparticles.
- To identify a core set of plasma MP proteins and investigate their correlation with patient demographics.
- To evaluate the potential of the plasma MP proteome as a source of disease biomarkers.
Main Methods:
- Label-free liquid chromatography coupled to tandem mass spectrometry was used to analyze plasma MP protein composition.
- High-confidence protein identification was achieved using SEQUEST XCor criteria.
- Analysis was performed on plasma samples from 42 patients, predominantly with cardiovascular disease.
Main Results:
- A total of 458 proteins were detected with high confidence in plasma MPs.
- A core set of 130 proteins was identified, consistently present across most patients.
- This core proteome is enriched in cytoskeletal, integrin complex, and hemostasis proteins.
- Spectral counts of some proteins correlated with patient age and gender.
Conclusions:
- The proteome of plasma microparticles represents a valuable and dependable source of biologically relevant disease biomarkers.
- The identified core set of MP proteins provides a foundation for further biomarker discovery.
- Plasma MP analysis holds promise for advancing diagnostic capabilities in various diseases.
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