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Comparative proteomic analysis of PAI-1 and TNF-alpha-derived endothelial microparticles. Proteomics 2008 Jun;8(12):2430-46 PMID: 18563738 PMCID: PMC4753841

Pubmed ID

18563738

DOI

10.1002/pmic.200701029

Abstract

Endothelium-derived microparticles (EMPs) are small vesicles released from endothelial cells in response to cell injury, apoptosis, or activation. Elevated concentrations of EMPs have been associated with many inflammatory and vascular diseases. EMPs also mediate long range signaling and alter downstream cell function. Unfortunately, the molecular and cellular basis of microparticle production and downstream cell function is poorly understood. We hypothesize that EMPs generated by different agonists will produce distinct populations of EMPs with unique protein compositions. To test this hypothesis, different EMP populations were generated from human umbilical vein endothelial cells by stimulation with plasminogen activator inhibitor type 1 (PAI-1) or tumor necrosis factor-alpha (TNF-alpha) and subjected to proteomic analysis by LC/MS. We identified 432 common proteins in all EMP populations studied. Also identified were 231 proteins unique to control EMPs, 104 proteins unique to PAI-1 EMPs and 70 proteins unique to TNF-alpha EMPs. Interestingly, variations in protein abundance were found among many of the common EMP proteins, suggesting that differences exist between EMPs on a relative scale. Finally, gene ontology (GO) and KEGG pathway analysis revealed many functional similarities and few differences between the EMP populations studied. In summary, our results clearly indicate that EMPs generated by PAI-1 and TNF-alpha produce EMPs with overlapping but distinct protein compositions. These observations provide fundamental insight into the mechanisms regulating the production of these particles and their physiological role in numerous diseases.

Author List

Peterson DB, Sander T, Kaul S, Wakim BT, Halligan B, Twigger S, Pritchard KA Jr, Oldham KT, Ou JS

Authors

Keith T. Oldham MD Professor in the Surgery department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




Scopus

2-s2.0-48249091633   99 Citations

MESH terms used to index this publication - Major topics in bold

Cell Culture Techniques
Cells, Cultured
Endothelial Cells
Endothelium, Vascular
Humans
Models, Biological
Particle Size
Plasminogen Activator Inhibitor 1
Proteomics
Tumor Necrosis Factor-alpha
Umbilical Veins
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad