HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Subodh Verma Richard D. Weisel Paul W. M. Fedak Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Verma, S. Articles by Mickle, D. A. G. Search for Related Content PubMed PubMed Citation Articles by Verma, S. Articles by Mickle, D. A. G. Related Collections Peripheral vascular

J Thorac Cardiovasc Surg 2003;126:1886-1891
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

C-reactive protein activates the nuclear factor-B signal transduction pathway in saphenous vein endothelial cells: implications for atherosclerosis and restenosis

^a Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada

Read at the Eighty-third Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 4-7, 2003.

Received for publication May 2, 2003; accepted for publication July 22, 2003.

^* Address for correspondence: Subodh Verma, MD, PhD, Division of Cardiac Surgery, 14 EN-215, 200 Elizabeth St, Toronto General Hospital, Toronto, ON, Canada M5G 2C4
subodh.verma{at}sympatico.ca

OBJECTIVES: Elevated levels of C-reactive protein are one of the strongest prognostic factors in atherosclerosis. In addition to predicting vascular disease, C-reactive protein may directly facilitate the development of a proinflammatory and proatherosclerotic phenotype. Recent studies have demonstrated marked up-regulation of various adhesion molecules and inflammatory responses in endothelial cells subjected to C-reactive protein. The nuclear factor-B signal transduction is known to play a key role in the expression of these proatherogenic entities. This study examines the direct effects of C-reactive protein on nuclear factor-B activation and related mechanisms in saphenous vein endothelial cells.

METHODS: The activation of nuclear factor-B was determined by confocal microscopy assessing the nuclear localization of nuclear factor-B in endothelial cells incubated with C-reactive protein (50 µg/mL) for 30 minutes and 3 hours. Cells not incubated with C-reactive protein were used as negative controls, and cells incubated with tumor necrosis factor- (10 ng/mL) for 15 minutes were used as positive controls in all studies. The degradation of IB- and IB-ß was assessed by Western blotting of the cell lysates obtained from cells incubated with human recombinant C-reactive protein (50 µg/mL) for 15 minutes, 30 minutes, and 1 hour.

RESULTS: Nuclear factor-B nuclear translocation in endothelial cells increased significantly after 30 minutes of incubation with C-reactive protein (P < .01). Nuclear localization of nuclear factor-B returned to baseline levels after 3 hours of incubation with C-reactive protein. Incubation with C-reactive protein resulted in degradation of IB- that was maximal at 30 minutes (P < .05). C-reactive protein showed no significant effect on IB-ß degradation.

CONCLUSIONS: These data demonstrate, for the first time, that C-reactive protein activates the nuclear factor-B signal transduction pathway in endothelial cells. Degradation of IB-, but not IB-ß, seems to be the major pathway leading to nuclear factor-B nuclear translocation and activation induced by C-reactive protein. These data support the concept that C-reactive protein, at concentrations known to predict diverse vascular insults, directly facilitates a proinflammatory and proatherosclerotic phenotype through activation of nuclear factor-B. These data have important implications for saphenous vein atherosclerosis in patients with elevated C-reactive protein levels.

This article has been cited by other articles:

				S. Emani, B. Ramlawi, N. R. Sodha, J. Li, C. Bianchi, and F. W. Sellke Increased vascular permeability after cardiopulmonary bypass in patients with diabetes is associated with increased expression of vascular endothelial growth factor and hepatocyte growth factor J. Thorac. Cardiovasc. Surg., July 1, 2009; 138(1): 185 - 191. [Abstract] [Full Text] [PDF]

				F. Lovren, Y. Pan, P. C. Shukla, A. Quan, H. Teoh, P. E. Szmitko, M. D. Peterson, M. Gupta, M. Al-Omran, and S. Verma Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1440 - E1449. [Abstract] [Full Text] [PDF]

				E. F. M. Wouters, K. H. Groenewegen, M. A. Dentener, and J. H. J. Vernooy Systemic Inflammation in Chronic Obstructive Pulmonary Disease: The Role of Exacerbations Proceedings of the ATS, December 1, 2007; 4(8): 626 - 634. [Abstract] [Full Text] [PDF]

				G. Liuzzo, M. Santamaria, L. M. Biasucci, M. Narducci, V. Colafrancesco, A. Porto, S. Brugaletta, M. Pinnelli, V. Rizzello, A. Maseri, et al. Persistent Activation of Nuclear Factor Kappa-B Signaling Pathway in Patients With Unstable Angina and Elevated Levels of C-Reactive Protein: Evidence for a Direct Proinflammatory Effect of Azide and Lipopolysaccharide-Free C-Reactive Protein on Human Monocytes Via Nuclear Factor Kappa-B Activation J. Am. Coll. Cardiol., January 16, 2007; 49(2): 185 - 194. [Abstract] [Full Text] [PDF]

				G. Cappabianca, D. Paparella, G. Visicchio, G. Capone, G. Lionetti, F. Numis, P. Ferrara, C. D'Agostino, and L. de Luca Tupputi Schinosa Preoperative C-Reactive Protein Predicts Mid-Term Outcome After Cardiac Surgery Ann. Thorac. Surg., December 1, 2006; 82(6): 2170 - 2178. [Abstract] [Full Text] [PDF]

				S. Devaraj, B. Davis, S. I. Simon, and I. Jialal CRP promotes monocyte-endothelial cell adhesion via Fc{gamma} receptors in human aortic endothelial cells under static and shear flow conditions Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1170 - H1176. [Abstract] [Full Text] [PDF]

				E. Paffen and M. P.M. deMaat C-reactive protein in atherosclerosis: A causal factor? Cardiovasc Res, July 1, 2006; 71(1): 30 - 39. [Abstract] [Full Text] [PDF]

				D.-H. Kang, S.-K. Park, I.-K. Lee, and R. J. Johnson Uric Acid-Induced C-Reactive Protein Expression: Implication on Cell Proliferation and Nitric Oxide Production of Human Vascular Cells J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3553 - 3562. [Abstract] [Full Text] [PDF]

				P. Cirillo, P. Golino, P. Calabro, G. Cali, M. Ragni, S. De Rosa, G. Cimmino, M. Pacileo, R. De Palma, L. Forte, et al. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation Cardiovasc Res, October 1, 2005; 68(1): 47 - 55. [Abstract] [Full Text] [PDF]

				T. Nakakuki, M. Ito, H. Iwasaki, Y. Kureishi, R. Okamoto, N. Moriki, M. Kongo, S. Kato, N. Yamada, N. Isaka, et al. Rho/Rho-Kinase Pathway Contributes to C-Reactive Protein-Induced Plasminogen Activator Inhibitor-1 Expression in Endothelial Cells Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2088 - 2093. [Abstract] [Full Text] [PDF]

				L. Li, N. Roumeliotis, T. Sawamura, and G. Renier C-Reactive Protein Enhances LOX-1 Expression in Human Aortic Endothelial Cells: Relevance of LOX-1 to C-Reactive Protein-Induced Endothelial Dysfunction Circ. Res., October 29, 2004; 95(9): 877 - 883. [Abstract] [Full Text] [PDF]

				S. Verma, M. A. Kuliszewski, S.-H. Li, P. E. Szmitko, L. Zucco, C.-H. Wang, M. V. Badiwala, D. A.G. Mickle, R. D. Weisel, P. W.M. Fedak, et al. C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function: Further Evidence of a Mechanistic Link Between C-Reactive Protein and Cardiovascular Disease Circulation, May 4, 2004; 109(17): 2058 - 2067. [Abstract] [Full Text] [PDF]

				S. Verma, P. E. Szmitko, and E. T.H. Yeh C-Reactive Protein: Structure Affects Function Circulation, April 27, 2004; 109(16): 1914 - 1917. [Full Text] [PDF]