© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide Modulates the Expression of Monocyte Chemoattractant Protein 1 in Cultured Human Endothelial Cells
From the Center of Physiology (B.F., B.S.-U., R.B.), University of Frankfurt, and the Department of Internal Medicine IV (A.M.Z.), Division of Cardiology, University of Frankfurt (Germany).
Correspondence to Andreas M. Zeiher, MD, Department of Internal Medicine IV, Division of Cardiology, University of Frankfurt, Theodor-Stern-Kai 7, Germany.
Abstract The recruitment of monocytes into the arterial wall
is one of the earliest events in the pathogenesis of atherosclerosis.
Since monocyte chemoattractant protein 1 (MCP-1) plays a key role in
the subendothelial recruitment of monocytes, we tested whether nitric
oxide (NO) modulates the expression of MCP-1 in cultured human
endothelial cells. Inhibition of basal NO production by
NG-nitro-L-arginine (L-NAG)
upregulates endothelial MCP-1 mRNA expression (250±20%) and protein
secretion. Exogenous addition of NO dose-dependently decreased MCP-1
mRNA expression and secretion. Changes in MCP-1 mRNA expression and
protein secretion were paralleled by corresponding changes in
chemotactic activity of cell-conditioned media for monocytes. An MCP-1
antibody reduced monocyte chemotactic activity by 85% and completely
abolished the increased monocyte chemotactic activity induced by the
inhibition of NO production. Elevation of endothelial cGMP levels had
no significant effect on MCP-1 mRNA expression. Inhibition of basal
endothelial NO production by L-NAG increased binding activity of a
nuclear factor 
B (NF-B)–like transcriptional regulatory factor,
whereas exogenous addition of NO decreased NF-B–like binding
activity during stimulation with tumor necrosis factor-
. Thus, NO
modulates MCP-1 expression and monocyte chemotactic activity secreted
by human umbilical vein endothelial cells (HUVECs) in culture. The
activation of NF-B–like transcriptional regulatory proteins by
inhibition of NO suggests a molecular link between an oxidant-sensitive
transcriptional regulatory mechanism and NO synthesis in HUVECs.
Key Words: nitric oxide • nuclear transcription factor • endothelial cells • monocyte chemoattractant protein 1 • atherosclerosis
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C. M. Hogaboam, C. S. Gallinat, C. Bone-Larson, S. W. Chensue, N. W. Lukacs, R. M. Strieter, and S. L. Kunkel Collagen Deposition in a Non-Fibrotic Lung Granuloma Model after Nitric Oxide Inhibition Am. J. Pathol., December 1, 1998; 153(6): 1861 - 1872. [Abstract] [Full Text] [PDF]
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K. M. Channon, H. Qian, V. Neplioueva, M. A. Blazing, E. Olmez, G. A. Shetty, S. A. Youngblood, J. Pawloski, T. McMahon, J. S. Stamler, et al. In Vivo Gene Transfer of Nitric Oxide Synthase Enhances Vasomotor Function in Carotid Arteries From Normal and Cholesterol-Fed Rabbits Circulation, November 3, 1998; 98(18): 1905 - 1911. [Abstract] [Full Text] [PDF]
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X.-L. Chen, P. E. Tummala, M. T. Olbrych, R. W. Alexander, and R. M. Medford Angiotensin II Induces Monocyte Chemoattractant Protein-1 Gene Expression in Rat Vascular Smooth Muscle Cells Circ. Res., November 2, 1998; 83(9): 952 - 959. [Abstract] [Full Text] [PDF]
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M. E. Ritchie Nuclear Factor-{kappa}B Is Selectively and Markedly Activated in Humans With Unstable Angina Pectoris Circulation, October 27, 1998; 98(17): 1707 - 1713. [Abstract] [Full Text] [PDF]
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D. Corseaux, T. Le Tourneau, I. Six, M. D. Ezekowitz, E. P. Mc Fadden, T. Meurice, P. Asseman, C. Bauters, and B. Jude Enhanced Monocyte Tissue Factor Response After Experimental Balloon Angioplasty in Hypercholesterolemic Rabbit: Inhibition With Dietary L-Arginine Circulation, October 27, 1998; 98(17): 1776 - 1782. [Abstract] [Full Text] [PDF]
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M. Katoh, K. Egashira, M. Usui, T. Ichiki, H. Tomita, H. Shimokawa, H. Rakugi, and A. Takeshita Cardiac Angiotensin II Receptors Are Upregulated by Long-Term Inhibition of Nitric Oxide Synthesis in Rats Circ. Res., October 5, 1998; 83(7): 743 - 751. [Abstract] [Full Text] [PDF]
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S. Pervin, R. Singh, M. E. Rosenfeld, M. Navab, G. Chaudhuri, and L. Nathan Estradiol Suppresses MCP-1 Expression In Vivo : Implications for Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1575 - 1582. [Abstract] [Full Text] [PDF]
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H. Tomita, K. Egashira, M. Kubo-Inoue, M. Usui, M. Koyanagi, H. Shimokawa, M. Takeya, T. Yoshimura, and A. Takeshita Inhibition of NO Synthesis Induces Inflammatory Changes and Monocyte Chemoattractant Protein-1 Expression in Rat Hearts and Vessels Arterioscler. Thromb. Vasc. Biol., September 1, 1998; 18(9): 1456 - 1464. [Abstract] [Full Text] [PDF]
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H. Tomita, K. Egashira, Y. Ohara, M. Takemoto, M. Koyanagi, M. Katoh, H. Yamamoto, K. Tamaki, H. Shimokawa, and A. Takeshita Early Induction of Transforming Growth Factor-ß via Angiotensin II Type 1 Receptors Contributes to Cardiac Fibrosis Induced by Long-term Blockade of Nitric Oxide Synthesis in Rats Hypertension, August 1, 1998; 32(2): 273 - 279. [Abstract] [Full Text] [PDF]
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S. Ravalli, A. Albala, M. Ming, M. Szabolcs, A. Barbone, R. E. Michler, and P. J. Cannon Inducible Nitric Oxide Synthase Expression in Smooth Muscle Cells and Macrophages of Human Transplant Coronary Artery Disease Circulation, June 16, 1998; 97(23): 2338 - 2345. [Abstract] [Full Text] [PDF]
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P. S. Tsao, J. Niebauer, R. Buitrago, P. S. Lin, B.-y. Wang, J. P. Cooke, Y-d. Ida Chen, and G. M. Reaven Interaction of Diabetes and Hypertension on Determinants of Endothelial Adhesiveness Arterioscler. Thromb. Vasc. Biol., June 1, 1998; 18(6): 947 - 953. [Abstract] [Full Text] [PDF]
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 D. Sekkai, F. Aillet, N. Israel, and M. Lepoivre Inhibition of NF-kappa B and HIV-1 Long Terminal Repeat Transcriptional Activation by Inducible Nitric Oxide Synthase 2 Activity J. Biol. Chem., February 13, 1998; 273(7): 3895 - 3900. [Abstract] [Full Text] [PDF]
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 C. M. Hogaboam, M. L. Steinhauser, H. Schock, N. Lukacs, R. M. Strieter, T. Standiford, and S. L. Kunkel Therapeutic Effects of Nitric Oxide Inhibition during Experimental Fecal Peritonitis: Role of Interleukin-10 and Monocyte Chemoattractant Protein 1 Infect. Immun., February 1, 1998; 66(2): 650 - 655. [Abstract] [Full Text] [PDF]
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J. S. Luoma, P. Stralin, S. L. Marklund, T. P. Hiltunen, T. Sarkioja, and S. Yla-Herttuala Expression of Extracellular SOD and iNOS in Macrophages and Smooth Muscle Cells in Human and Rabbit Atherosclerotic Lesions : Colocalization With Epitopes Characteristic of Oxidized LDL and Peroxynitrite-Modified Proteins Arterioscler. Thromb. Vasc. Biol., February 1, 1998; 18(2): 157 - 167. [Abstract] [Full Text] [PDF]
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C. Hermann, A. M. Zeiher, and S. Dimmeler Shear Stress Inhibits H2O2-Induced Apoptosis of Human Endothelial Cells by Modulation of the Glutathione Redox Cycle and Nitric Oxide Synthase Arterioscler. Thromb. Vasc. Biol., December 1, 1997; 17(12): 3588 - 3592. [Abstract] [Full Text]
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V. Guetta, A. A. Quyyumi, A. Prasad, J. A. Panza, M. Waclawiw, and R. O. Cannon III The Role of Nitric Oxide in Coronary Vascular Effects of Estrogen in Postmenopausal Women Circulation, November 4, 1997; 96(9): 2795 - 2801. [Abstract] [Full Text]
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P. Skarsgard, C. Van Breemen, and I. Laher Estrogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide Am J Physiol Heart Circ Physiol, November 1, 1997; 273(5): H2248 - H2256. [Abstract] [Full Text] [PDF]
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T. Marumo, V. B. Schini-Kerth, B. Fisslthaler, and R. Busse Platelet-Derived Growth Factor–Stimulated Superoxide Anion Production Modulates Activation of Transcription Factor NF-{kappa}B and Expression of Monocyte Chemoattractant Protein 1 in Human Aortic Smooth Muscle Cells Circulation, October 7, 1997; 96(7): 2361 - 2367. [Abstract] [Full Text]
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J.-L. Balligand and P. J. Cannon Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 1846 - 1858. [Abstract] [Full Text]
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M. J. Thomassen, L. T. Buhrow, M. J. Connors, F. Kaneko, S. C. Erzurum, and M. S. Kavuru Nitric Oxide Inhibits Inflammatory Cytokine Production by Human Alveolar Macrophages Am. J. Respir. Cell Mol. Biol., September 1, 1997; 17(3): 279 - 283. [Abstract] [Full Text]
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S. P. Schwarzacher, T. T. Lim, B. Wang, R. S. Kernoff, J. Niebauer, J. P. Cooke, and A. C. Yeung Local Intramural Delivery of L-Arginine Enhances Nitric Oxide Generation and Inhibits Lesion Formation After Balloon Angioplasty Circulation, April 1, 1997; 95(7): 1863 - 1869. [Abstract] [Full Text]
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M. Hernandez-Presa, C. Bustos, M. Ortego, J. Tunon, G. Renedo, M. Ruiz-Ortega, and J. Egido Angiotensin-Converting Enzyme Inhibition Prevents Arterial Nuclear Factor-{kappa}B Activation, Monocyte Chemoattractant Protein-1 Expression, and Macrophage Infiltration in a Rabbit Model of Early Accelerated Atherosclerosis Circulation, March 18, 1997; 95(6): 1532 - 1541. [Abstract] [Full Text]
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M. R. Adams, W. Jessup, D. Hailstones, and D. S. Celermajer L-Arginine Reduces Human Monocyte Adhesion to Vascular Endothelium and Endothelial Expression of Cell Adhesion Molecules Circulation, February 4, 1997; 95(3): 662 - 668. [Abstract] [Full Text]
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 E. Allaire and A. W. Clowes Endothelial Cell Injury in Cardiovascular Surgery: The Intimal Hyperplastic Response Ann. Thorac. Surg., February 1, 1997; 63(2): 582 - 591. [Abstract] [Full Text]
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J. P. Cooke and P. S. Tsao Arginine: A New Therapy for Atherosclerosis? Circulation, January 21, 1997; 95(2): 311 - 312. [Full Text]
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W. Aji, S. Ravalli, M. Szabolcs, X.-c. Jiang, R. R. Sciacca, R. E. Michler, and P. J. Cannon L-Arginine Prevents Xanthoma Development and Inhibits Atherosclerosis in LDL Receptor Knockout Mice Circulation, January 21, 1997; 95(2): 430 - 437. [Abstract] [Full Text]
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W. Schaper and W. D. Ito Molecular Mechanisms of Coronary Collateral Vessel Growth Circ. Res., November 1, 1996; 79(5): 911 - 919. [Full Text]
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P. S. Tsao, R. Buitrago, J. R. Chan, and J. P. Cooke Fluid Flow Inhibits Endothelial Adhesiveness: Nitric Oxide and Transcriptional Regulation of VCAM-1 Circulation, October 1, 1996; 94(7): 1682 - 1689. [Abstract] [Full Text]
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R. C. Candipan, B.-y. Wang, R. Buitrago, P. S. Tsao, and J. P. Cooke Regression or Progression : Dependency on Vascular Nitric Oxide Arterioscler. Thromb. Vasc. Biol., January 1, 1996; 16(1): 44 - 50. [Abstract] [Full Text]
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