C-reactive protein impairs the endothelial glycocalyx resulting in endothelial dysfunction

Sridevi Devaraj, Jung Mi Yun, Grete Adamson, Jose Galvez, Ishwarlal Jialal

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

AimsInflammation is pivotal in atherosclerosis and a key early step is endothelial dysfunction. C-reactive protein, the prototypic marker of inflammation, and cardiovascular risk marker have been shown to promote atherogenesis. Increased levels of C-reactive protein are associated with endothelial dysfunction. The glycocalyx decorates the luminal surface and affords critical protection of the endothelium. Thus, the aim of the study was to examine the effect of C-reactive protein on the endothelial glycocalyx.Methods and resultsHuman aortic endothelial cells (HAECs) were incubated with C-reactive protein at different concentrations (0, 12.5, 25, and 50 g/mL) with boiled C-reactive protein as a control. For in vivo experiments, human C-reactive protein was injected into rats and human serum albumin was used as a control. Endothelial glycocalyx thickness was examined by transmission electron microscopy. Hyaluronan (HA) was examined in the supernatant of HAECs and in plasma and surface expression of heparan sulfate (HS) was quantified. C-reactive protein dose-dependently increased HA release in vitro and in vivo (P < 0.01). Also, glycocalyx thickness was significantly decreased (P < 0.05). Western blotting for HS showed significant reduction in expression of HS, one of the main glycosaminoglycans in the glycocalyx, with C-reactive protein treatment. There was a significant positive correlation between HA release and monocyte-endothelial cell adhesion, plasminogen activator inhibitor-1, and intercellular adhesion molecule-1 release and a negative correlation with endothelial nitric oxide synthase activity.ConclusionCollectively, these data suggest that C-reactive protein impairs glycocalyx function, resulting in endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalCardiovascular Research
Volume84
Issue number3
DOIs
StatePublished - 2009

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Glycocalyx
C-Reactive Protein
Heparitin Sulfate
Hyaluronic Acid
Atherosclerosis
Endothelial Cells
Nitric Oxide Synthase Type III
Plasminogen Activator Inhibitor 1
Intercellular Adhesion Molecule-1
Glycosaminoglycans
Transmission Electron Microscopy
Cell Adhesion
Serum Albumin
Endothelium
Monocytes
Western Blotting
Inflammation

Keywords

  • C-reactive protein
  • Dysfunction
  • Endothelium
  • ENOS
  • Glycocalyx
  • Hyaluronan
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

C-reactive protein impairs the endothelial glycocalyx resulting in endothelial dysfunction. / Devaraj, Sridevi; Yun, Jung Mi; Adamson, Grete; Galvez, Jose; Jialal, Ishwarlal.

In: Cardiovascular Research, Vol. 84, No. 3, 2009, p. 479-484.

Research output: Contribution to journalArticle

Devaraj, Sridevi ; Yun, Jung Mi ; Adamson, Grete ; Galvez, Jose ; Jialal, Ishwarlal. / C-reactive protein impairs the endothelial glycocalyx resulting in endothelial dysfunction. In: Cardiovascular Research. 2009 ; Vol. 84, No. 3. pp. 479-484.
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