C-reactive protein induces VCAM-1 gene expression through NF-kappaB activation in vascular endothelial cells

Atherosclerosis. 2006 Mar;185(1):39-46. doi: 10.1016/j.atherosclerosis.2005.01.057. Epub 2005 Jul 5.


Recent studies have shown that C-reactive protein (CRP) is not just a predictor of cardiovascular events but also acts directly as a proinflammatory stimulus in vascular cells. In this report, we studied the molecular mechanisms underlying vascular cellular adhesion molecule-1 (VCAM-1) induction by CRP. CRP-induced VCAM-1 mRNA expression and this induction was inhibited by protein kinase C (PKC) inhibitors, p38 mitogen-activated protein kinase (MAPK) inhibitor, and tyrosine kinase inhibitors. In addition, parthenolide, a nuclear factor kappaB (NF-kappaB) inhibitor, abolished VCAM-1 induction. Moreover, CRP increased VCAM-1 promoter activity, indicating that CRP induces VCAM-1 mRNA expression at the transcriptional level. Mutation of NF-kappaB-binding sites resulted in a loss of induction. Finally, an electrophoretic mobility shift assay confirmed binding of the p65 subunit of NF-kappaB to kappaB-binding sites. Taken together, our findings suggest that VCAM-1 induction by CRP is mediated by PKC, p38MAPK, tyrosine kinase and the NF-kappaB-dependent signaling pathways in vascular endothelial cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Blotting, Northern
  • C-Reactive Protein / pharmacology*
  • Cattle
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Gene Expression*
  • Humans
  • In Vitro Techniques
  • Mutation
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • RNA, Messenger / genetics*
  • Signal Transduction / physiology
  • Transcriptional Activation / drug effects
  • Vascular Cell Adhesion Molecule-1 / biosynthesis
  • Vascular Cell Adhesion Molecule-1 / genetics*


  • NF-kappa B
  • RNA, Messenger
  • Vascular Cell Adhesion Molecule-1
  • C-Reactive Protein