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

• Published in: Atherosclerosis Vol. 185; no. 1; pp. 39 - 46
• Main Authors: Kawanami, Daiji, Maemura, Koji, Takeda, Norihiko, Harada, Tomohiro, Nojiri, Takefumi, Saito, Tetsuya, Manabe, Ichiro, Imai, Yasushi, Nagai, Ryozo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.03.2006; Elsevier
• Subjects: Associated diseases and complications; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial function; Fundamental and applied biological sciences. Psychology; Inflammation; Medical sciences; Vertebrates: cardiovascular system; Inflammation; Atherosclerosis; Endothelial function; Endothelial cell; Protein kinase C; Stimulus; Enzyme; Transferases; Cell adhesion molecule; Mitogen-activated protein kinase; Mobility; Cardiovascular disease; Gene expression; Vascular disease; Mutation; C reactive protein; Protein-tyrosine kinase
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2005.01.057

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 κB (NF-κB) 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-κB-binding sites resulted in a loss of induction. Finally, an electrophoretic mobility shift assay confirmed binding of the p65 subunit of NF-κB to κB-binding sites. Taken together, our findings suggest that VCAM-1 induction by CRP is mediated by PKC, p38MAPK, tyrosine kinase and the NF-κB-dependent signaling pathways in vascular endothelial cells.