(Circulation. 1997;95:1532-1541.)
© 1997 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme Inhibition Prevents Arterial Nuclear Factor-
B Activation, Monocyte Chemoattractant Protein-1 Expression, and Macrophage Infiltration in a Rabbit Model of Early Accelerated Atherosclerosis
From the Research Laboratory (M.H.-P., C.B., M.O., M.R.-O., J.E.), Division of Cardiology (J.T.), and Department of Pathology (G.R.), Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.
Correspondence to Jesús Egido, MD, Research Laboratories, Fundación Jiménez Díaz, Avda Reyes Católicos 2, 28040 Madrid, Spain. E-mail egido{at}alpha2.ft.uam.es
Background The migration of monocytes into the vessel wall is
a critical event leading to the development of atherosclerosis.
Monocyte chemoattractant protein-1 (MCP-1) is the main chemotactic
factor involved in this phenomenon, and nuclear factor-
B (NF-B)
is one of the nuclear factors controlling its expression. ACE
inhibitors have been useful in some experimental models of
atherosclerosis. In this work, we addressed the hypothesis that
angiotensin II (Ang II) may be implicated in the recruitment of
monocytes into the vessel wall through the activation of NF-B and
the induction of MCP-1 expression.
Methods and Results Accelerated atherosclerosis was induced
in the femoral arteries of rabbits by endothelial desiccation and
atherogenic diet for 7 days. Atherosclerotic vessels exhibited an
increase in NF-B–like activity, and p50 and p65 NF-B subunits
were identified as components of this activity. MCP-1 (mRNA and
protein) was also expressed in the injured vessels coincidently with
the neointimal macrophage infiltration. ACE inhibition with quinapril
reduced these three parameters. In cultured monocytic and vascular
smooth muscle cells, Ang II elicited an increase in NF-B activation
and MCP-1 expression that was prevented by preincubation of cells with
pyrrolidinedithiocarbamate, an inhibitor of NF-B activation.
Conclusions The present data support a role for Ang II in
neointimal monocyte infiltration through NF-B activation and MCP-1
expression in a model of accelerated atherosclerosis in rabbits. Our
results suggest that ACE inhibitors may have a beneficial effect in
early atherosclerosis.
Key Words: angiotensin • atherosclerosis • molecular biology • immunohistochemistry
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 A. J. P. Lewington, M. Arici, K. P. G. Harris, N. J. Brunskill, and J. Walls Modulation of the renin-angiotensin system in proteinuric renal disease: are there added benefits? Nephrol. Dial. Transplant., May 1, 2001; 16(5): 885 - 888. [Full Text] [PDF]
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M. Katoh, K. Egashira, C. Kataoka, M. Usui, M. Koyanagi, S. Kitamoto, Y. Ohmachi, A. Takeshita, and H. Narita Regression by ACE inhibition of arteriosclerotic changes induced by chronic blockade of NO synthesis in rats Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2306 - H2312. [Abstract] [Full Text] [PDF]
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M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, J. Blanco, and J. Egido Systemic Infusion of Angiotensin II into Normal Rats Activates Nuclear Factor-{{kappa}}B and AP-1 in the Kidney : Role of AT1 and AT2 Receptors Am. J. Pathol., May 1, 2001; 158(5): 1743 - 1756. [Abstract] [Full Text] [PDF]
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G. G. Bishop, J. A. McPherson, J. M. Sanders, S. E. Hesselbacher, M. J. Feldman, C. A. McNamara, L. W. Gimple, E. R. Powers, S. A. Mousa, and I. J. Sarembock Selective {{alpha}}v{beta}3-Receptor Blockade Reduces Macrophage Infiltration and Restenosis After Balloon Angioplasty in the Atherosclerotic Rabbit Circulation, April 10, 2001; 103(14): 1906 - 1911. [Abstract] [Full Text] [PDF]
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V. J. Dzau Tissue Angiotensin and Pathobiology of Vascular Disease : A Unifying Hypothesis Hypertension, April 1, 2001; 37(4): 1047 - 1052. [Abstract] [Full Text] [PDF]
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D. Gomez-Garre, R. Largo, N. Tejera, J. Fortes, F. Manzarbeitia, and J. Egido Activation of NF-{{kappa}}B in Tubular Epithelial Cells of Rats With Intense Proteinuria : Role of Angiotensin II and Endothelin-1 Hypertension, April 1, 2001; 37(4): 1171 - 1178. [Abstract] [Full Text] [PDF]
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M. SATOH, N. KASHIHARA, Y. YAMASAKI, K. MARUYAMA, K. OKAMOTO, Y. MAESHIMA, H. SUGIYAMA, T. SUGAYA, K. MURAKAMI, and H. MAKINO Renal Interstitial Fibrosis Is Reduced in Angiotensin II Type 1a Receptor-Deficient Mice J. Am. Soc. Nephrol., February 1, 2001; 12(2): 317 - 325. [Abstract] [Full Text]
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U. Kintscher, S. Wakino, S. Kim, E. Fleck, W. A. Hsueh, and R. E. Law Angiotensin II Induces Migration and Pyk2/Paxillin Phosphorylation of Human Monocytes Hypertension, February 1, 2001; 37(2): 587 - 593. [Abstract] [Full Text] [PDF]
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F. C. Luft Workshop: Mechanisms and Cardiovascular Damage in Hypertension Hypertension, February 1, 2001; 37(2): 594 - 598. [Abstract] [Full Text] [PDF]
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S. Raiden, Y. Pereyra, V. Nahmod, C. Alvarez, L. Castello, M. Giordano, and J. Geffner Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP J. Leukoc. Biol., November 1, 2000; 68(5): 700 - 706. [Abstract] [Full Text]
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L. Piqueras, P. Kubes, A. Alvarez, E. O'Connor, A. C. Issekutz, J. V. Esplugues, and M.-J. Sanz Angiotensin II Induces Leukocyte-Endothelial Cell Interactions In Vivo Via AT1 and AT2 Receptor-Mediated P-Selectin Upregulation Circulation, October 24, 2000; 102(17): 2118 - 2123. [Abstract] [Full Text] [PDF]
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D. Li, T. Saldeen, F. Romeo, and J. L. Mehta Oxidized LDL Upregulates Angiotensin II Type 1 Receptor Expression in Cultured Human Coronary Artery Endothelial Cells : The Potential Role of Transcription Factor NF-{kappa}B Circulation, October 17, 2000; 102(16): 1970 - 1976. [Abstract] [Full Text] [PDF]
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E. Bush, N. Maeda, W. A. Kuziel, T. C. Dawson, J. N. Wilcox, H. DeLeon, and W. R. Taylor CC Chemokine Receptor 2 Is Required for Macrophage Infiltration and Vascular Hypertrophy in Angiotensin II-Induced Hypertension Hypertension, September 1, 2000; 36(3): 360 - 363. [Abstract] [Full Text] [PDF]
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L. M. Blanco-Colio, M. Valderrama, L. A. Alvarez-Sala, C. Bustos, M. Ortego, M. A. Hernandez-Presa, P. Cancelas, J. Gomez-Gerique, J. Millan, and J. Egido Red Wine Intake Prevents Nuclear Factor-{kappa}B Activation in Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia Circulation, August 29, 2000; 102(9): 1020 - 1026. [Abstract] [Full Text] [PDF]
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S. Kitamoto, K. Egashira, C. Kataoka, M. Koyanagi, M. Katoh, H. Shimokawa, R. Morishita, Y. Kaneda, K. Sueishi, and A. Takeshita Increased Activity of Nuclear Factor-{kappa}B Participates in Cardiovascular Remodeling Induced by Chronic Inhibition of Nitric Oxide Synthesis in Rats Circulation, August 15, 2000; 102(7): 806 - 812. [Abstract] [Full Text] [PDF]
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W. Gonzalez, V. Fontaine, M. E. Pueyo, N. Laquay, D. Messika-Zeitoun, M. Philippe, J.-F. Arnal, M.-P. Jacob, and J.-B. Michel Molecular Plasticity of Vascular Wall During NG-Nitro-L-Arginine Methyl Ester-Induced Hypertension : Modulation of Proinflammatory Signals Hypertension, July 1, 2000; 36(1): 103 - 109. [Abstract] [Full Text] [PDF]
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M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, S. Konig, B. Wittig, and J. Egido Angiotensin II Activates Nuclear Transcription Factor {kappa}B Through AT1 and AT2 in Vascular Smooth Muscle Cells : Molecular Mechanisms Circ. Res., June 23, 2000; 86(12): 1266 - 1272. [Abstract] [Full Text] [PDF]
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M. Ruiz-Ortega, O. Lorenzo, M. Ruperez, and J. Egido ACE inhibitors and AT1 receptor antagonists--beyond the haemodynamic effect Nephrol. Dial. Transplant., May 1, 2000; 15(5): 561 - 565. [Full Text] [PDF]
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M. Klouche, S. Rose-John, W. Schmiedt, and S. Bhakdi Enzymatically Degraded, Nonoxidized LDL Induces Human Vascular Smooth Muscle Cell Activation, Foam Cell Transformation, and Proliferation Circulation, April 18, 2000; 101(15): 1799 - 1805. [Abstract] [Full Text] [PDF]
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D. Li and J. L. Mehta Upregulation of Endothelial Receptor for Oxidized LDL (LOX-1) by Oxidized LDL and Implications in Apoptosis of Human Coronary Artery Endothelial Cells : Evidence From Use of Antisense LOX-1 mRNA and Chemical Inhibitors Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1116 - 1122. [Abstract] [Full Text] [PDF]
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B. Schieffer, E. Schieffer, D. Hilfiker-Kleiner, A. Hilfiker, P. T. Kovanen, M. Kaartinen, J. Nussberger, W. Harringer, and H. Drexler Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques : Potential Implications for Inflammation and Plaque Instability Circulation, March 28, 2000; 101(12): 1372 - 1378. [Abstract] [Full Text] [PDF]
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W. B Strawn, R. H Dean, and C. M Ferrario Novel mechanisms linking angiotensin II and early atherogenesis Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1): 11 - 17. [PDF]
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E. Napoleone, A. Di Santo, M. Camera, E. Tremoli, and R. Lorenzet Angiotensin-Converting Enzyme Inhibitors Downregulate Tissue Factor Synthesis in Monocytes Circ. Res., February 4, 2000; 86(2): 139 - 143. [Abstract] [Full Text] [PDF]
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M. Usui, K. Egashira, H. Tomita, M. Koyanagi, M. Katoh, H. Shimokawa, M. Takeya, T. Yoshimura, K. Matsushima, and A. Takeshita Important Role of Local Angiotensin II Activity Mediated via Type 1 Receptor in the Pathogenesis of Cardiovascular Inflammatory Changes Induced by Chronic Blockade of Nitric Oxide Synthesis in Rats Circulation, January 25, 2000; 101(3): 305 - 310. [Abstract] [Full Text] [PDF]
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C. E. Donovan, D. A. Mark, H. Z. He, H.-C. Liou, L. Kobzik, Y. Wang, G. T. De Sanctis, D. L. Perkins, and P. W. Finn NF-{kappa}B/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation J. Immunol., December 15, 1999; 163(12): 6827 - 6833. [Abstract] [Full Text] [PDF]
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H. Soejima, H. Ogawa, H. Yasue, K. Kaikita, K. Takazoe, K. Nishiyama, K. Misumi, S. Miyamoto, M. Yoshimura, K. Kugiyama, et al. Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction J. Am. Coll. Cardiol., October 1, 1999; 34(4): 983 - 988. [Abstract] [Full Text] [PDF]
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R. Kranzhofer, J. Schmidt, C. A. H. Pfeiffer, S. Hagl, P. Libby, and W. Kubler Angiotensin Induces Inflammatory Activation of Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1623 - 1629. [Abstract] [Full Text] [PDF]
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A. Nicoletti and J.-B. Michel Cardiac fibrosis and inflammation: interaction with hemodynamic and hormonal factors Cardiovasc Res, March 1, 1999; 41(3): 532 - 543. [Abstract] [Full Text] [PDF]
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R. Largo, D. Gomez-Garre, K. Soto, B. Marron, J. Blanco, R. M. Gazapo, J. J. Plaza, and J. Egido Angiotensin-Converting Enzyme Is Upregulated in the Proximal Tubules of Rats With Intense Proteinuria Hypertension, February 1, 1999; 33(2): 732 - 739. [Abstract] [Full Text] [PDF]
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F. C. Luft, E. Mervaala, D. N. Muller, V. Gross, F. Schmidt, J. K. Park, C. Schmitz, A. Lippoldt, V. Breu, R. Dechend, et al. Hypertension-Induced End-Organ Damage : A New Transgenic Approach to an Old Problem Hypertension, January 1, 1999; 33(1): 212 - 218. [Abstract] [Full Text] [PDF]
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C. Bustos, M. A. Hernandez-Presa, M.o. Ortego, J. Tunon, L. Ortega, F. Perez, C. Diaz, G. Hernandez, and J. Egido HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis J. Am. Coll. Cardiol., December 1, 1998; 32(7): 2057 - 2064. [Abstract] [Full Text] [PDF]
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M. A. Hernandez-Presa, C. Bustos, M. Ortego, J. Tunon, L. Ortega, and J. Egido ACE Inhibitor Quinapril Reduces the Arterial Expression of NF-{kappa}B-Dependent Proinflammatory Factors but not of Collagen I in a Rabbit Model of Atherosclerosis Am. J. Pathol., December 1, 1998; 153(6): 1825 - 1837. [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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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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M. Klouche, S. Gottschling, V. Gerl, W. Hell, M. Husmann, B. Dorweiler, M. Messner, and S. Bhakdi Atherogenic Properties of Enzymatically Degraded LDL : Selective Induction of MCP-1 and Cytotoxic Effects on Human Macrophages Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1376 - 1385. [Abstract] [Full Text] [PDF]
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