Lovastatin reduces nuclear factor kappaB activation induced by C-reactive protein in human vascular endothelial cells.
The role of C-reactive protein (CRP) in atherogenesis has been supported by more recent data. Some studies have demonstrated marked up-regulation inflammatory responses in endothelial cells subjected to CRP. The nuclear factor-kappaB (NF-kappaB) signal transduction is known to play a key role in the expression of these proatherogenic entities. Statins have anti-inflammatory properties independent of their cholesterol-lowering effects. Therefore, we studied the effects of CRP and lovastatin on NF-kappaB activation in human umbilical vein endothelial cells (HUVECs). By using an electrophoretic mobility shift assays (EMSA), we found that CRP (50 microg/ml) increased activation of NF-kappaB and degradation of inhibitory kappa B (IkappaB) in HUVECs, reaching a maximal effect after the incubation with CRP for 1 h. Lovastatin (10(-5) mol/l) diminished NF-kappaB activation induced by CRP. Furthermore, lovastatin may block NF-kappaB activation by causing a stabilization of the IkappaB-alpha in cellular cytoplasm with western blotting analysis. Preincubation of HUVECs with pyrrolidinethiocarbamate (PDTC, NF-kappaB inhibitor) diminished CD40 expression induced by CRP with flow cytometry. Our results suggest that CRP increases activation of NF-kappaB and induces CD40 expression in HUVECs partly via activation of NF-kappaB. Lovastatin, through the inhibition of NF-kappaB activation, reduces the inflammation involved in the pathogenesis of atherosclerosis.
Lin
Rong
R
Department of Pharmacology, Xi'an Jiaotong University School of Medical, Xi'an Shaanxi, P.R. China. linrong@mail.xjtu.edu.cn
Liu
Juntian
J
Peng
Ning
N
Yang
Guangde
G
Gan
Weijie
W
Wang
Weirong
W
D015153:Blotting, Western; D002097:C-Reactive Protein / Q000096:biosynthesis*; D019013:CD40 Antigens; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D019013:CD40 Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020672:I-kappa B Proteins; D016328:NF-kappa B; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D002097:C-Reactive Protein; D011392:Proline; D008148:Lovastatin