Endothelin Antagonism and Interleukin-6 Inhibition Attenuate the Proatherogenic Effects of C-Reactive Protein
- 23 April 2002
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 105 (16), 1890-1896
- https://doi.org/10.1161/01.cir.0000015126.83143.b4
Abstract
Background — C-reactive protein (CRP) has been suggested to actively participate in the development of atherosclerosis. In the present study, we examined the role of the potent endothelium-derived vasoactive factor endothelin-1 (ET-1) and the inflammatory cytokine interleukin-6 (IL-6) as mediators of CRP-induced proatherogenic processes. Methods and Results — Saphenous vein endothelial cells (HSVECs) were incubated with human recombinant CRP (25 μg/mL, 24 hours) and the expression of vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1), and monocyte chemoattractant chemokine-1 was determined. The effects of CRP on LDL uptake were assessed in macrophages using immunofluorescent labeling of CD32 and CD14. In each study, the effect of endothelin antagonism (bosentan) and IL-6 inhibition (monoclonal anti-IL-6 antibodies) was examined. The effects of CRP on the secretion of ET-1 and IL-6 from HSVECs were also evaluated. Incubation of HSVECs with recombinant human CRP resulted in a marked increase in ICAM-1 and VCAM-1 expression ( P P P P P Conclusions — CRP actively promotes a proatherosclerotic and proinflammatory phenotype. These effects are mediated, in part, via the production of ET-1 and IL-6 and are attenuated by mixed ET A/B receptor antagonism and IL-6 inhibition. Bosentan may be useful in decreasing CRP-mediated vascular disease.Keywords
This publication has 18 references indexed in Scilit:
- High sensitivity C-reactive protein for predicting cardiovascular disease: an inflammatory hypothesisEuropean Heart Journal, 2001
- AtherosclerosisCell, 2001
- Atherosclerosis: cell biology and lipoproteinsCurrent Opinion in Lipidology, 2000
- C-Reactive Protein and Other Markers of Inflammation in the Prediction of Cardiovascular Disease in WomenNew England Journal of Medicine, 2000
- Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?Atherosclerosis, 2000
- Atherosclerosis — An Inflammatory DiseaseNew England Journal of Medicine, 1999
- Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha.JCI Insight, 1997
- Role of IL-6 and Its Soluble Receptor in Induction of Chemokines and Leukocyte RecruitmentImmunity, 1997
- VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes.JCI Insight, 1993
- Induction of inflammatory cytokine release from cultured human monocytes by C-reactive proteinCytokine, 1992