C-reactive protein impairs the endothelial glycocalyx resulting in endothelial dysfunction.
OBJECTIVE
Inflammation 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.


RESULTS
Human aortic endothelial cells (HAECs) were incubated with C-reactive protein at different concentrations (0, 12.5, 25, and 50 microg/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.


CONCLUSIONS
Collectively, these data suggest that C-reactive protein impairs glycocalyx function, resulting in endothelial dysfunction.
Devaraj
Sridevi
S
Laboratory for Atherosclerosis and Metabolic Research, Department of Medical Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA.
Yun
Jung-Mi
JM
Adamson
Grete
G
Galvez
Jose
J
Jialal
Ishwarlal
I
D001011:Aorta / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D019276:Glycocalyx / Q000378:metabolism* / Q000648:ultrastructure; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism
D015415:Biomarkers; D002097:C-Reactive Protein; D006497:Heparan Sulfate; D006820:Hyaluronic Acid