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Circulation. 2000;102:2165-2168

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(Circulation. 2000;102:2165.)
© 2000 American Heart Association, Inc.


Brief Rapid Communications

Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells

Vincenzo Pasceri, MD; James T. Willerson, MD; Edward T. H. Yeh, MD

From the Department of Cardiology (E.T.H.Y.), University of Texas–M.D. Anderson Cancer Center, Houston, Tex; Department of Internal Medicine (V.P., J.T.W., E.T.H.Y.) and Institute of Molecular Medicine for the Prevention of Human Diseases (E.T.H.Y.), University of Texas Health Science Center, Houston, Tex; and the Texas Heart Institute (V.P., J.T.W., E.T.H.Y.), St. Luke’s Episcopal Hospital, Houston, Tex.

Correspondence to Edward T.H. Yeh, MD, Department of Cardiology, 1515 Holcombe Blvd, Box 70, University of Texas–M.D. Anderson Cancer Center, Houston, TX 77030-4095.

Background—The acute-phase reactant C-reactive protein (CRP) is an important risk factor for coronary heart disease. However, the possible effects of CRP on vascular cells are not known.

Methods and Results—We tested the effects of CRP on expression of adhesion molecules in both human umbilical vein and coronary artery endothelial cells. Expression of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and E-selectin was assessed by flow cytometry. Incubation with recombinant human CRP (10 µg/mL) for 24 hours induced an {approx}10-fold increase in expression of ICAM-1 and a significant expression of VCAM-1, whereas a 6-hour incubation induced significant E-selectin expression. Adhesion molecule induction was similar to that observed in endothelial cells activated with interleukin-1ß. In coronary artery endothelial cells, induction of ICAM-1 and VCAM-1 was already present at 5 µg/mL and reached a maximum at 50 µg/mL, at which point a substantial increase in expression of E-selectin was also evident. The CRP effect was dependent on presence of human serum in the culture medium, because no effect was seen in cells cultured with serum-free medium. In contrast, interleukin-1ß was able to induce adhesion molecule expression in the absence of human serum.

Conclusions—CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis and present a potential target for the treatment of atherosclerosis.


Key Words: cell adhesion molecules • endothelium • atherosclerosis




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Arterioscler. Thromb. Vasc. Bio.Home page
S. Kapiotis, G. Holzer, G. Schaller, M. Haumer, H. Widhalm, D. Weghuber, B. Jilma, G. Roggla, M. Wolzt, K. Widhalm, et al.
A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes
Arterioscler Thromb Vasc Biol, November 1, 2006; 26(11): 2541 - 2546.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
M. Rahmani, R. P. Cruz, D. J. Granville, and B. M. McManus
Allograft Vasculopathy Versus Atherosclerosis
Circ. Res., October 13, 2006; 99(8): 801 - 815.
[Abstract] [Full Text] [PDF]


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Nephrol Dial TransplantHome page
P. Stenvinkel
C-reactive protein--does it promote vascular disease?
Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2718 - 2720.
[Full Text] [PDF]


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StrokeHome page
E. Van De Graaff, M. Dutta, P. Das, E. A. Shry, P. D. Frederick, M. Blaney, D. J. Pasta, and S. R. Steinhubl
Early Coronary Revascularization Diminishes the Risk of Ischemic Stroke With Acute Myocardial Infarction
Stroke, October 1, 2006; 37(10): 2546 - 2551.
[Abstract] [Full Text] [PDF]


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StrokeHome page
J. I. Suarez
Acute Myocardial Infarction, Ischemic Stroke, Sympathetic Stress, and Inflammation: Birds of a Feather
Stroke, October 1, 2006; 37(10): 2449 - 2450.
[Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
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]


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ANGIOLOGYHome page
M. Suzuki, M. Saito, T. Nagai, H. Saeki, and Y. Kazatani
Systemic Versus Coronary Levels of Inflammation in Acute Coronary Syndromes
Angiology, August 1, 2006; 57(4): 459 - 463.
[Abstract] [PDF]


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Eur J Heart FailHome page
I. Kovacs, J. Toth, J. Tarjan, and A. Koller
Correlation of flow mediated dilation with inflammatory markers in patients with impaired cardiac function. Beneficial effects of inhibition of ACE
Eur J Heart Fail, August 1, 2006; 8(5): 451 - 459.
[Abstract] [Full Text] [PDF]


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Int J EpidemiolHome page
J. P Casas, T. Shah, J. Cooper, E. Hawe, A. D McMahon, D. Gaffney, C. J Packard, D. S O'Reilly, I. Juhan-Vague, J. S Yudkin, et al.
Insight into the nature of the CRP-coronary event association using Mendelian randomization
Int. J. Epidemiol., August 1, 2006; 35(4): 922 - 931.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
M. Juonala, J. S.A. Viikari, T. Ronnemaa, L. Taittonen, J. Marniemi, and O. T. Raitakari
Childhood C-Reactive Protein in Predicting CRP and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study
Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1883 - 1888.
[Abstract] [Full Text] [PDF]


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CirculationHome page
D. A. Morrow, J. A. de Lemos, M. S. Sabatine, S. D. Wiviott, M. A. Blazing, A. Shui, N. Rifai, R. M. Califf, and E. Braunwald
Clinical Relevance of C-Reactive Protein During Follow-Up of Patients With Acute Coronary Syndromes in the Aggrastat-to-Zocor Trial
Circulation, July 25, 2006; 114(4): 281 - 288.
[Abstract] [Full Text] [PDF]


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ANN INTERN MEDHome page
D. M. Lloyd-Jones, K. Liu, L. Tian, and P. Greenland
Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease
Ann Intern Med, July 4, 2006; 145(1): 35 - 42.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
L. M. Biasucci and V. Rizzello
Pregnancy-associated plasma protein-a: do specific markers of vascular or plaque activation exist, and do we really need them?
Clin. Chem., June 1, 2006; 52(6): 913 - 914.
[Full Text] [PDF]


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Int ImmunolHome page
M. Oroszlan, E. Herczenik, S. Rugonfalvi-Kiss, A. Roos, A. J Nauta, M. R Daha, I. Gombos, I. Karadi, L. Romics, Z. Prohaszka, et al.
Proinflammatory changes in human umbilical cord vein endothelial cells can be induced neither by native nor by modified CRP
Int. Immunol., June 1, 2006; 18(6): 871 - 878.
[Abstract] [Full Text] [PDF]


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Hum ReprodHome page
M. Hemelaar, P. Kenemans, C.G. Schalkwijk, D.D.M. Braat, and M.J. van der Mooren
No increase in C-reactive protein levels during intranasal compared to oral hormone therapy in healthy post-menopausal women
Hum. Reprod., June 1, 2006; 21(6): 1635 - 1642.
[Abstract] [Full Text] [PDF]


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CirculationHome page
B. M. Scirica, D. A. Morrow, S. Verma, S. Devaraj, I. Jialal, B. M. Scirica, D. A. Morrow, S. Verma, S. Devaraj, and I. Jialal
The Verdict Is Still Out
Circulation, May 2, 2006; 113(17): 2128 - 2151.
[Full Text] [PDF]


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ANGIOLOGYHome page
A. Guven, A. Cetinkaya, M. Aral, G. Sokmen, M. A. Buyukbese, A. Guven, and N. Koksal
High-Sensitivity C-Reactive Protein in Patients with Metabolic Syndrome
Angiology, May 1, 2006; 57(3): 295 - 302.
[Abstract] [PDF]


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Psychosom. Med.Home page
M. Hamer, E. Williams, R. Vuonovirta, P. Giacobazzi, E. L. Gibson, and A. Steptoe
The Effects of Effort-Reward Imbalance on Inflammatory and Cardiovascular Responses to Mental Stress
Psychosom Med, May 1, 2006; 68(3): 408 - 413.
[Abstract] [Full Text] [PDF]


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StrokeHome page
J. Montaner, I. Fernandez-Cadenas, C. A. Molina, M. Ribo, R. Huertas, A. Rosell, A. Penalba, L. Ortega, P. Chacon, and J. Alvarez-Sabin
Poststroke C-Reactive Protein Is a Powerful Prognostic Tool Among Candidates for Thrombolysis
Stroke, May 1, 2006; 37(5): 1205 - 1210.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J.-a Kim, M. Montagnani, K. K. Koh, and M. J. Quon
Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms
Circulation, April 18, 2006; 113(15): 1888 - 1904.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
I. Montero, J. Orbe, N. Varo, O. Beloqui, J. I. Monreal, J. A. Rodriguez, J. Diez, P. Libby, and J. A. Paramo
C-Reactive Protein Induces Matrix Metalloproteinase-1 and -10 in Human Endothelial Cells: Implications for Clinical and Subclinical Atherosclerosis
J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1369 - 1378.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
I. Jialal, S. Devaraj, and U. Singh
C-Reactive Protein and the Vascular Endothelium: Implications for Plaque Instability
J. Am. Coll. Cardiol., April 4, 2006; 47(7): 1379 - 1381.
[Full Text] [PDF]


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Eur J EndocrinolHome page
J. Bollerslev, T. Ueland, A. P Jorgensen, K. J Fougner, R. Wergeland, T. Schreiner, and P. Burman
Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency.
Eur. J. Endocrinol., April 1, 2006; 154(4): 537 - 543.
[Abstract] [Full Text] [PDF]


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ChestHome page
L. M. O'Brien, L. D. Serpero, R. Tauman, and D. Gozal
Plasma adhesion molecules in children with sleep-disordered breathing.
Chest, April 1, 2006; 129(4): 947 - 953.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
P. Minoretti, C. Falcone, M. Calcagnino, E. Emanuele, M. P. Buzzi, E. Coen, and D. Geroldi
Prognostic significance of plasma osteopontin levels in patients with chronic stable angina
Eur. Heart J., April 1, 2006; 27(7): 802 - 807.
[Abstract] [Full Text] [PDF]


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Nephrol Dial TransplantHome page
M. Hermann and F. Ruschitzka
Novel anti-inflammatory drugs in hypertension
Nephrol. Dial. Transplant., April 1, 2006; 21(4): 859 - 864.
[Full Text] [PDF]


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Physiol. Rev.Home page
A. Tedgui and Z. Mallat
Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways
Physiol Rev, April 1, 2006; 86(2): 515 - 581.
[Abstract] [Full Text] [PDF]


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HeartHome page
D Tousoulis, M Charakida, and C Stefanadis
Endothelial function and inflammation in coronary artery disease
Heart, April 1, 2006; 92(4): 441 - 444.
[Abstract] [Full Text] [PDF]


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Ann Rheum DisHome page
K M J Douglas, A V Pace, G J Treharne, A Saratzis, P Nightingale, N Erb, M J Banks, and G D Kitas
Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome
Ann Rheum Dis, March 1, 2006; 65(3): 348 - 353.
[Abstract] [Full Text] [PDF]


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CirculationHome page
E. J. Armstrong, D. A. Morrow, and M. S. Sabatine
Inflammatory Biomarkers in Acute Coronary Syndromes: Part II: Acute-Phase Reactants and Biomarkers of Endothelial Cell Activation
Circulation, February 21, 2006; 113(7): e152 - e155.
[Full Text] [PDF]