Plasma Levels of Endothelial Microparticles Bearing Monomeric C-reactive Protein are Increased in Peripheral Artery Disease

J Cardiovasc Transl Res. 2016 Jun;9(3):184-193. doi: 10.1007/s12265-016-9678-0. Epub 2016 Feb 18.


C-reactive protein (CRP) as an indicator of cardiovascular disease (CVD) has shown limited sensitivity. We demonstrate that two isoforms of CRP (pentameric, pCRP and monomeric, mCRP) present in soluble form or on microparticles (MPs) have different biological effects and are not all measured by clinical CRP assays. The high-sensitivity CRP assay (hsCRP) did not measure pCRP or mCRP on MPs, whereas flow cytometry did. MPs derived from endothelial cells, particularly those bearing mCRP, were elevated in peripheral artery disease (PAD) patients compared to controls. The numbers of mCRP(+) endothelial MPs did not correlate with hsCRP measurements of soluble pCRP, indicating their independent modulation. In controls, statins lowered mCRP(+) endothelial MPs. In a model of vascular inflammation, mCRP induced endothelial shedding of MPs and was proinflammatory, while pCRP was anti-inflammatory. mCRP on endothelial MPs may be both an unmeasured indicator of, and an amplifier of, vascular disease, and its detection might improve risk sensitivity.

Keywords: CRP; Inflammation; Microparticle; Monomeric CRP; Pentameric CRP; Peripheral artery disease; hsCRP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Case-Control Studies
  • Cell-Derived Microparticles / drug effects
  • Cell-Derived Microparticles / metabolism*
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / diagnosis
  • Peripheral Arterial Disease / drug therapy
  • Pilot Projects
  • Up-Regulation


  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Inflammation Mediators
  • C-Reactive Protein