(Circulation. 1995;91:2125-2131.)
© 1995 American Heart Association, Inc.
Articles |
Identification of 92-kD Gelatinase in Human Coronary Atherosclerotic Lesions
Association of Active Enzyme Synthesis With Unstable Angina
Presented in part at the 43rd Scientific Session of the American College of Cardiology, Atlanta, Ga, March 13-17, 1994.
From the Division of Cardiovascular Medicine, University of California, San Diego Medical Center (D.L.B.); the Rheumatology Division, Veterans Affairs Medical Center, Newington, Conn (M.S.H.); and the Division of Cardiology, St Elizabeth's Hospital, Boston, Mass (M.K., C.L., J.M.I.).
Correspondence to David L. Brown, MD, Division of Cardiovascular Medicine, University of California, San Diego, 200 W Arbor, San Diego, CA 92103-8411.
Background Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia.
Methods and Results Coronary atherectomy specimens from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture (unstable angina) (n=12) were immunostained for the presence of 92-kD gelatinase; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis and angina but without acute ischemia (stable angina) (n=12). Positive immunostaining for 92-kD gelatinase was present in 83% of specimens from both unstable and stable angina patients. However, intracellular localization of enzyme (indicating active synthesis) was documented in 10 of 10 positively stained specimens from patients with unstable angina compared with 3 of 10 positively stained specimens from patients with stable angina. Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by immunostaining of adjacent sections.
Conclusions 92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions. Active synthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia.
Key Words: atherosclerosis • angina • coronary disease
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D. P. Mason, R. D. Kenagy, D. Hasenstab, D. F. Bowen-Pope, R. A. Seifert, S. Coats, S. M. Hawkins, and A. W. Clowes Matrix Metalloproteinase-9 Overexpression Enhances Vascular Smooth Muscle Cell Migration and Alters Remodeling in the Injured Rat Carotid Artery Circ. Res., December 3, 1999; 85(12): 1179 - 1185. [Abstract] [Full Text] [PDF]
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J Mann and M J Davies Mechanisms of progression in native coronary artery disease: role of healed plaque disruption Heart, September 1, 1999; 82(3): 265 - 268. [Abstract] [Full Text] [PDF]
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A. Bini, K. G. Mann, B. J. Kudryk, and F. J. Schoen Noncollagenous Bone Matrix Proteins, Calcification, and Thrombosis in Carotid Artery Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 1999; 19(8): 1852 - 1861. [Abstract] [Full Text] [PDF]
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T. B. Rajavashisth, X.-P. Xu, S. Jovinge, S. Meisel, X.-O. Xu, N.-N. Chai, M. C. Fishbein, S. Kaul, B. Cercek, B. Sharifi, et al. Membrane Type 1 Matrix Metalloproteinase Expression in Human Atherosclerotic Plaques : Evidence for Activation by Proinflammatory Mediators Circulation, June 22, 1999; 99(24): 3103 - 3109. [Abstract] [Full Text] [PDF]
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B. Zhang, S. Ye, S.-M. Herrmann, P. Eriksson, M. de Maat, A. Evans, D. Arveiler, G. Luc, F. Cambien, A. Hamsten, et al. Functional Polymorphism in the Regulatory Region of Gelatinase B Gene in Relation to Severity of Coronary Atherosclerosis Circulation, April 13, 1999; 99(14): 1788 - 1794. [Abstract] [Full Text] [PDF]
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 A. P. Burke, A. Farb, G. T. Malcom, Y.-h. Liang, J. E. Smialek, and R. Virmani Plaque Rupture and Sudden Death Related to Exertion in Men With Coronary Artery Disease JAMA, March 10, 1999; 281(10): 921 - 926. [Abstract] [Full Text] [PDF]
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X.-P. Xu, S. R. Meisel, J. M. Ong, S. Kaul, B. Cercek, T. B. Rajavashisth, B. Sharifi, and P. K. Shah Oxidized Low-Density Lipoprotein Regulates Matrix Metalloproteinase-9 and Its Tissue Inhibitor in Human Monocyte-Derived Macrophages Circulation, March 2, 1999; 99(8): 993 - 998. [Abstract] [Full Text] [PDF]
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 U. Schonbeck, F. Mach, G. K. Sukhova, E. Atkinson, E. Levesque, M. Herman, P. Graber, P. Basset, and P. Libby Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40-CD40 Ligand Signaling In Vitro and In Vivo J. Exp. Med., March 1, 1999; 189(5): 843 - 853. [Abstract] [Full Text] [PDF]
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A. C. van der Wal and A. E. Becker Atherosclerotic plaque rupture - pathologic basis of plaque stability and instability Cardiovasc Res, February 1, 1999; 41(2): 334 - 344. [Full Text] [PDF]
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R. Rabbani and E. J. Topol Strategies to achieve coronary arterial plaque stabilization Cardiovasc Res, February 1, 1999; 41(2): 402 - 417. [Abstract] [Full Text] [PDF]
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G. Bauriedel, R. Hutter, U. Welsch, R. Bach, H. Sievert, and B. Luderitz Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability Cardiovasc Res, February 1, 1999; 41(2): 480 - 488. [Abstract] [Full Text] [PDF]
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N. Marx, U. Schonbeck, M. A. Lazar, P. Libby, and J. Plutzky Peroxisome Proliferator-Activated Receptor Gamma Activators Inhibit Gene Expression and Migration in Human Vascular Smooth Muscle Cells Circ. Res., November 30, 1998; 83(11): 1097 - 1103. [Abstract] [Full Text] [PDF]
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M. Aikawa, E. Rabkin, S. J. Voglic, H. Shing, R. Nagai, F. J. Schoen, and P. Libby Lipid Lowering Promotes Accumulation of Mature Smooth Muscle Cells Expressing Smooth Muscle Myosin Heavy Chain Isoforms in Rabbit Atheroma Circ. Res., November 16, 1998; 83(10): 1015 - 1026. [Abstract] [Full Text] [PDF]
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S. Bellosta, D. Via, M. Canavesi, P. Pfister, R. Fumagalli, R. Paoletti, and F. Bernini HMG-CoA Reductase Inhibitors Reduce MMP-9 Secretion by Macrophages Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1671 - 1678. [Abstract] [Full Text] [PDF]
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M. Kaartinen, A. C. van der Wal, C. M. van der Loos, J. J. Piek, K. T. Koch, A. E. Becker, and P. T. Kovanen Mast cell infiltration in acute coronary syndromes: implications for plaque rupture J. Am. Coll. Cardiol., September 1, 1998; 32(3): 606 - 612. [Abstract] [Full Text] [PDF]
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R. P. Fabunmi, G. K. Sukhova, S. Sugiyama, and P. Libby Expression of Tissue Inhibitor of Metalloproteinases-3 in Human Atheroma and Regulation in Lesion-Associated Cells : A Potential Protective Mechanism in Plaque Stability Circ. Res., August 10, 1998; 83(3): 270 - 278. [Abstract] [Full Text] [PDF]
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H. Kai, H. Ikeda, H. Yasukawa, M. Kai, Y. Seki, F. Kuwahara, T. Ueno, K. Sugi, and T. Imaizumi Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes J. Am. Coll. Cardiol., August 1, 1998; 32(2): 368 - 372. [Abstract] [Full Text] [PDF]
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P. K Shah Role of inflammation and metalloproteinases in plaque disruption and thrombosis Vascular Medicine, August 1, 1998; 3(3): 199 - 206. [Abstract] [PDF]
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 P. T. Kovanen, M. Manttari, T. Palosuo, V. Manninen, and K. Aho Prediction of Myocardial Infarction in Dyslipidemic Men by Elevated Levels of Immunoglobulin Classes A, E, and G, but Not M Arch Intern Med, July 13, 1998; 158(13): 1434 - 1439. [Abstract] [Full Text]
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M.J. Davies Reactive Oxygen Species, Metalloproteinases, and Plaque Stability Circulation, June 23, 1998; 97(24): 2382 - 2383. [Full Text] [PDF]
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M. Aikawa, E. Rabkin, Y. Okada, S. J. Voglic, S. K. Clinton, C. E. Brinckerhoff, G. K. Sukhova, and P. Libby Lipid Lowering by Diet Reduces Matrix Metalloproteinase Activity and Increases Collagen Content of Rabbit Atheroma : A Potential Mechanism of Lesion Stabilization Circulation, June 23, 1998; 97(24): 2433 - 2444. [Abstract] [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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R. B. Wesley II, X. Meng, D. Godin, and Z. S. Galis Extracellular Matrix Modulates Macrophage Functions Characteristic to Atheroma : Collagen Type I Enhances Acquisition of Resident Macrophage Traits by Human Peripheral Blood Monocytes In Vitro Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 432 - 440. [Abstract] [Full Text] [PDF]
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R. T. Lee and P. Libby The Unstable Atheroma Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1859 - 1867. [Full Text]
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U. Schonbeck, F. Mach, G. K. Sukhova, C. Murphy, J.-Y. Bonnefoy, R. P. Fabunmi, and P. Libby Regulation of Matrix Metalloproteinase Expression in Human Vascular Smooth Muscle Cells by T Lymphocytes : A Role for CD40 Signaling in Plaque Rupture? Circ. Res., September 19, 1997; 81(3): 448 - 454. [Abstract] [Full Text]
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K. E. Webb, A. M. Henney, S. Anglin, S. E. Humphries, and J. R. McEwan Expression of Matrix Metalloproteinases and Their Inhibitor TIMP-1 in the Rat Carotid Artery After Balloon Injury Arterioscler Thromb Vasc Biol, September 1, 1997; 17(9): 1837 - 1844. [Abstract] [Full Text]
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M. Kaartinen, A. Penttila, and P. T. Kovanen Mast Cells in Rupture-Prone Areas of Human Coronary Atheromas Produce and Store TNF-{alpha} Circulation, December 1, 1996; 94(11): 2787 - 2792. [Abstract] [Full Text]
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R.D. Kenagy, S. Vergel, E. Mattsson, M. Bendeck, M.A. Reidy, and A.W. Clowes The Role of Plasminogen, Plasminogen Activators, and Matrix Metalloproteinases in Primate Arterial Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, November 1, 1996; 16(11): 1373 - 1382. [Abstract] [Full Text]
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M. J. Davies Stability and Instability: Two Faces of Coronary Atherosclerosis: The Paul Dudley White Lecture 1995 Circulation, October 15, 1996; 94(8): 2013 - 2020. [Full Text]
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S. Ye, P. Eriksson, A. Hamsten, M. Kurkinen, S. E. Humphries, and A. M. Henney Progression of Coronary Atherosclerosis Is Associated with a Common Genetic Variant of the Human Stromelysin-1 Promoter Which Results in Reduced Gene Expression J. Biol. Chem., May 31, 1996; 271(22): 13055 - 13060. [Abstract] [Full Text] [PDF]
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N. Zempo, N. Koyama, R. D. Kenagy, H. J. Lea, and A. W. Clowes Regulation of Vascular Smooth Muscle Cell Migration and Proliferation In Vitro and in Injured Rat Arteries by a Synthetic Matrix Metalloproteinase Inhibitor Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 28 - 33. [Abstract] [Full Text]
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C. M. Dollery, J. R. McEwan, and A. M. Henney Matrix Metalloproteinases and Cardiovascular Disease Circ. Res., November 1, 1995; 77(5): 863 - 868. [Full Text]
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P. T. Kovanen, M. Kaartinen, and T. Paavonen Infiltrates of Activated Mast Cells at the Site of Coronary Atheromatous Erosion or Rupture in Myocardial Infarction Circulation, September 1, 1995; 92(5): 1084 - 1088. [Abstract] [Full Text]
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