Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1145-1151
© 1995 American Heart Association, Inc.
Articles |
Inflammation and Matrix Metalloproteinases in the Enlarging Abdominal Aortic Aneurysm
From the Departments of Biochemistry (T.F., R.J.T., J.T.P.), Histopathology (A.C.), and Surgery (D.J.H., R.M.G., J.T.P.), Charing Cross and Westminster Medical School, London, UK.
Correspondence to Dr J.T. Powell, Department of Surgery, Charing Cross Hospital, Fulham Palace Rd, London W6 8RF, UK.
Abstract The risk of rupture of an abdominal aortic aneurysm increases with aortic diameter. To obtain insight into the pathological processes associated with the vascular remodeling that accompanies aortic dilatation, we compared the histological features and the activity of matrix metalloproteinases (MMPs) in biopsies from 21 small (4.0 to 5.5 cm in diameter) and 45 larger abdominal aortic aneurysms. The histological feature most clearly associated with enlarging aneurysm diameter was a higher density of inflammatory cells in the adventitia, P=.018. This inflammation was nonspecific, principally macrophages and B lymphocytes. Fibrosis of the adventitia provided compensatory thickening of the aortic wall as the aneurysm diameter increased. A combination of zymography and immunoblotting identified gelatinase A (MMP-2) as the principal metallogelatinase in small aneurysms, whereas zymography indicated an increasing activity of gelatinase B (MMP-9) in large aneurysms. Homogenates prepared from both small and large aneurysms had similar total activity against gelatin or type IV collagen. However, the concentration of gelatinase A, determined by immunoassay, was highest for small aneurysms: median concentrations, 385, 244, and 166 ng/mg protein for small aneurysms, large aneurysms, and atherosclerotic aorta, respectively. Immunolocalization studies indicated that gelatinase A was concentrated along fibrous tissue of both the acellular media and the atherosclerotic plaque. The recruitment of inflammatory cells into the adventitia, with subsequent elaboration of metalloproteinases, including gelatinase B, may contribute to the rapid growth and rupture of larger aneurysms.
Key Words: aortic aneurysm • gelatinase A • inflammation • matrix remodeling
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Y.-X. Wang, B. Martin-McNulty, A. D. Freay, D. A. Sukovich, M. Halks-Miller, W.-W. Li, R. Vergona, M. E. Sullivan, J. Morser, W. P. Dole, et al. Angiotensin II Increases Urokinase-Type Plasminogen Activator Expression and Induces Aneurysm in the Abdominal Aorta of Apolipoprotein E-Deficient Mice Am. J. Pathol., October 1, 2001; 159(4): 1455 - 1464. [Abstract] [Full Text]
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G. Sangiorgi, R. D'Averio, A. Mauriello, M. Bondio, M. Pontillo, S. Castelvecchio, S. Trimarchi, V. Tolva, G. Nano, V. Rampoldi, et al. Plasma Levels of Metalloproteinases-3 and -9 as Markers of Successful Abdominal Aortic Aneurysm Exclusion After Endovascular Graft Treatment Circulation, September 18, 2001; 104 (2009): I-288 - I-295. [Abstract] [Full Text] [PDF]
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J.-B. Michel Contrasting Outcomes of Atheroma Evolution: Intimal Accumulation Versus Medial Destruction Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1389 - 1392. [Full Text] [PDF]
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B. Zhang, S. Dhillon, I. Geary, W. M. Howell, F. Iannotti, I. N.M. Day, and S. Ye Polymorphisms in Matrix Metalloproteinase-1, -3, -9, and -12 Genes in Relation to Subarachnoid Hemorrhage Stroke, September 1, 2001; 32(9): 2198 - 2202. [Abstract] [Full Text] [PDF]
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P. Schoenhagen, K. M. Ziada, D. G. Vince, S. E. Nissen, and E. M. Tuzcu Arterial remodeling and coronary artery disease: the concept of "dilated" versus "obstructive" coronary atherosclerosis J. Am. Coll. Cardiol., August 1, 2001; 38(2): 297 - 306. [Abstract] [Full Text] [PDF]
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S. Goodall, M. Crowther, D. M. Hemingway, P. R. Bell, and M. M. Thompson Ubiquitous Elevation of Matrix Metalloproteinase-2 Expression in the Vasculature of Patients With Abdominal Aneurysms Circulation, July 17, 2001; 104(3): 304 - 309. [Abstract] [Full Text] [PDF]
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K.G. Jones, D.J. Brull, L.C. Brown, M. Sian, R.M. Greenhalgh, S.E. Humphries, and J.T. Powell Interleukin-6 (IL-6) and the Prognosis of Abdominal Aortic Aneurysms Circulation, May 8, 2001; 103(18): 2260 - 2265. [Abstract] [Full Text] [PDF]
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Y. L. Song, J. W. Ford, D. Gordon, and C. J. Shanley Regulation of Lysyl Oxidase by Interferon-{gamma} in Rat Aortic Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2000; 20(4): 982 - 988. [Abstract] [Full Text] [PDF]
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G. Plenz, A. Dorszewski, W. Volker, Y. S. Ko, N. J. Severs, G. Breithardt, and H. Robenek Cholesterol-Induced Changes of Type VIII Collagen Expression and Distribution in Carotid Arteries of Rabbit Arterioscler. Thromb. Vasc. Biol., October 1, 1999; 19(10): 2395 - 2404. [Abstract] [Full Text] [PDF]
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L. J. Walton, I. J. Franklin, T. Bayston, L. C. Brown, R. M. Greenhalgh, G. W. Taylor, and J. T. Powell Inhibition of Prostaglandin E2 Synthesis in Abdominal Aortic Aneurysms : Implications for Smooth Muscle Cell Viability, Inflammatory Processes, and the Expansion of Abdominal Aortic Aneurysms Circulation, July 6, 1999; 100(1): 48 - 54. [Abstract] [Full Text] [PDF]
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L. E. P. Rohde, L. H. Arroyo, N. Rifai, M. A. Creager, P. Libby, P. M. Ridker, and R. T. Lee Plasma Concentrations of Interleukin-6 and Abdominal Aortic Diameter Among Subjects Without Aortic Dilatation Arterioscler. Thromb. Vasc. Biol., July 1, 1999; 19(7): 1695 - 1699. [Abstract] [Full Text] [PDF]
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 R.W. Thompson, S. Liao, and J.A. Curci Therapeutic Potential of Tetracycline Derivatives to Suppress the Growth of Abdominal Aortic Aneurysms Advances in Dental Research, November 1, 1998; 12(1): 159 - 165. [Abstract] [PDF]
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R. Mohan, W. B. Rinehart, P. Bargagna-Mohan, and M. E. Fini Gelatinase B/lacZ Transgenic Mice, a Model for Mapping Gelatinase B Expression during Developmental and Injury-related Tissue Remodeling J. Biol. Chem., October 2, 1998; 273(40): 25903 - 25914. [Abstract] [Full Text] [PDF]
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V. Davis, R. Persidskaia, L. Baca-Regen, Y. Itoh, H. Nagase, Y. Persidsky, A. Ghorpade, and B. T. Baxter Matrix Metalloproteinase-2 Production and Its Binding to the Matrix Are Increased in Abdominal Aortic Aneurysms Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1625 - 1633. [Abstract] [Full Text] [PDF]
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U. Schonbeck, F. Mach, and P. Libby Generation of Biologically Active IL-1{beta} by Matrix Metalloproteinases: A Novel Caspase-1-Independent Pathway of IL-1{beta} Processing J. Immunol., October 1, 1998; 161(7): 3340 - 3346. [Abstract] [Full Text] [PDF]
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D. R. Todor, I. Lewis, G. Bruno, and D. Chyatte Identification of a Serum Gelatinase Associated With the Occurrence of Cerebral Aneurysms as Pro-Matrix Metalloproteinase-2 Stroke, August 1, 1998; 29(8): 1580 - 1583. [Abstract] [Full Text] [PDF]
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M.J. Davies Aortic Aneurysm Formation : Lessons From Human Studies and Experimental Models Circulation, July 21, 1998; 98(3): 193 - 195. [Full Text] [PDF]
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Z. S. Galis, K. Asanuma, D. Godin, and X. Meng N-Acetyl-Cysteine Decreases the Matrix-Degrading Capacity of Macrophage-Derived Foam Cells : New Target for Antioxidant Therapy? Circulation, June 23, 1998; 97(24): 2445 - 2453. [Abstract] [Full Text] [PDF]
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J. Juvonen, H.-M. Surcel, J. Satta, A.-M. Teppo, A. Bloigu, H. Syrjala, J. Airaksinen, M. Leinonen, P. Saikku, and T. Juvonen Elevated Circulating Levels of Inflammatory Cytokines in Patients With Abdominal Aortic Aneurysm Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 2843 - 2847. [Abstract] [Full Text]
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P. K. Shah Inflammation, Metalloproteinases, and Increased Proteolysis : An Emerging Pathophysiological Paradigm in Aortic Aneurysm Circulation, October 7, 1997; 96(7): 2115 - 2117. [Full Text]
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W. D. McMillan, N. A. Tamarina, M. Cipollone, D. A. Johnson, M. A. Parker, and W. H. Pearce Size Matters : The Relationship Between MMP-9 Expression and Aortic Diameter Circulation, October 7, 1997; 96(7): 2228 - 2232. [Abstract] [Full Text]
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C. E. Ruiz, H. P. Zhang, A. I. Butt, and P. Whittaker Percutaneous Treatment of Abdominal Aortic Aneurysm in a Swine Model : Understanding the Behavior of Aortic Aneurysm Closure Through a Serial Histopathological Analysis Circulation, October 7, 1997; 96(7): 2438 - 2448. [Abstract] [Full Text]
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W. D. Coats, P. Whittaker, D. T. Cheung, J. W. Currier, B. Han, and D. P. Faxon Collagen Content Is Significantly Lower in Restenotic Versus Nonrestenotic Vessels After Balloon Angioplasty in the Atherosclerotic Rabbit Model Circulation, March 4, 1997; 95(5): 1293 - 1300. [Abstract] [Full Text]
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J. B. Knox, G. K. Sukhova, A. D. Whittemore, and P. Libby Evidence for Altered Balance Between Matrix Metalloproteinases and Their Inhibitors in Human Aortic Diseases Circulation, January 7, 1997; 95(1): 205 - 212. [Abstract] [Full Text]
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T. Freestone, R.J. Turner, D.J. Higman, M.J. Lever, and J.T. Powell Influence of Hypercholesterolemia and Adventitial Inflammation on the Development of Aortic Aneurysm in Rabbits Arterioscler. Thromb. Vasc. Biol., January 1, 1997; 17(1): 10 - 17. [Abstract] [Full Text]
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S. W. Galt, S. Lindemann, D. Medd, L. L. Allen, L. W. Kraiss, E. S. Harris, S. M. Prescott, T. M. McIntyre, A. S. Weyrich, and G. A. Zimmerman Differential Regulation of Matrix Metalloproteinase-9 by Monocytes Adherent to Collagen and Platelets Circ. Res., September 14, 2001; 89(6): 509 - 516. [Abstract] [Full Text] [PDF]
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F. J. Miller Jr, W. J. Sharp, X. Fang, L. W. Oberley, T. D. Oberley, and N. L. Weintraub Oxidative Stress in Human Abdominal Aortic Aneurysms: A Potential Mediator of Aneurysmal Remodeling Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 560 - 565. [Abstract] [Full Text] [PDF]
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