This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, D. L. Articles by Isner, J. M. Search for Related Content PubMed PubMed Citation Articles by Brown, D. L. Articles by Isner, J. M.

(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.

David L. Brown, MD; Margaret S. Hibbs, MD; Marianne Kearney, BS; Carrie Loushin, BS; Jeffrey M. Isner, MD

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

This article has been cited by other articles:

				S. Yamada, K.-Y. Wang, A. Tanimoto, J. Fan, S. Shimajiri, S. Kitajima, M. Morimoto, M. Tsutsui, T. Watanabe, K. Yasumoto, et al. Matrix Metalloproteinase 12 Accelerates the Initiation of Atherosclerosis and Stimulates the Progression of Fatty Streaks to Fibrous Plaques in Transgenic Rabbits Am. J. Pathol., May 1, 2008; 172(5): 1419 - 1429. [Abstract] [Full Text] [PDF]

				E. Lancelot, V. Amirbekian, I. Brigger, J.-S. Raynaud, S. Ballet, C. David, O. Rousseaux, S. Le Greneur, M. Port, H. R. Lijnen, et al. Evaluation of Matrix Metalloproteinases in Atherosclerosis Using a Novel Noninvasive Imaging Approach Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 425 - 432. [Abstract] [Full Text] [PDF]

				M. Taurino, S. Raffa, M. Mastroddi, V. Visco, L. Rizzo, M. R. Torrisi, and V. Faraglia Metalloproteinase Expression in Carotid Plaque and Its Correlation With Plasma Levels Before and After Carotid Endarterectomy Vascular and Endovascular Surgery, January 1, 2008; 41(6): 516 - 521. [Abstract] [PDF]

				A. Leclercq, X. Houard, M. Philippe, V. Ollivier, U. Sebbag, O. Meilhac, and J.-B. Michel Involvement of intraplaque hemorrhage in atherothrombosis evolution via neutrophil protease enrichment J. Leukoc. Biol., December 1, 2007; 82(6): 1420 - 1429. [Abstract] [Full Text] [PDF]

				N. Eldrup, M.-L. M. Gronholdt, H. Sillesen, and B. G. Nordestgaard Elevated Matrix Metalloproteinase-9 Associated With Stroke or Cardiovascular Death in Patients With Carotid Stenosis Circulation, October 24, 2006; 114(17): 1847 - 1854. [Abstract] [Full Text] [PDF]

				J. Herrmann, L. O. Lerman, D. Mukhopadhyay, C. Napoli, and A. Lerman Angiogenesis in Atherogenesis Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 1948 - 1957. [Abstract] [Full Text] [PDF]

				M. Papaspyridonos, A. Smith, K. G. Burnand, P. Taylor, S. Padayachee, K. E. Suckling, C. H. James, D. R. Greaves, and L. Patel Novel Candidate Genes in Unstable Areas of Human Atherosclerotic Plaques Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1837 - 1844. [Abstract] [Full Text] [PDF]

				L. Nilsson, L. Jonasson, J. Nijm, A. Hamsten, and P. Eriksson Increased Plasma Concentration of Matrix Metalloproteinase-7 in Patients with Coronary Artery Disease Clin. Chem., August 1, 2006; 52(8): 1522 - 1527. [Abstract] [Full Text] [PDF]

				J.-o Deguchi, M. Aikawa, C.-H. Tung, E. Aikawa, D.-E. Kim, V. Ntziachristos, R. Weissleder, and P. Libby Inflammation in Atherosclerosis: Visualizing Matrix Metalloproteinase Action in Macrophages In Vivo Circulation, July 4, 2006; 114(1): 55 - 62. [Abstract] [Full Text] [PDF]

				N. Fiotti, N. Altamura, M. Fisicaro, N. Carraro, L. Uxa, G. Grassi, L. Torelli, R. Gobbato, G. Guarnieri, B. T. Baxter, et al. MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1330 - 1336. [Abstract] [Full Text] [PDF]

				A. C. Newby Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates Cardiovasc Res, February 15, 2006; 69(3): 614 - 624. [Abstract] [Full Text] [PDF]

				R. Schmidt, A. Bultmann, M. Ungerer, N. Joghetaei, O. Bulbul, S. Thieme, T. Chavakis, B. P. Toole, M. Gawaz, A. Schomig, et al. Extracellular Matrix Metalloproteinase Inducer Regulates Matrix Metalloproteinase Activity in Cardiovascular Cells: Implications in Acute Myocardial Infarction Circulation, February 14, 2006; 113(6): 834 - 841. [Abstract] [Full Text] [PDF]

				S. Agewall Matrix metalloproteinases and cardiovascular disease Eur. Heart J., January 2, 2006; 27(2): 121 - 122. [Full Text] [PDF]

				G Arno, J C Kaski, D A Smith, J P Akiyu, S E Hughes, and C Baboonian Matrix metalloproteinase-9 expression is associated with the presence of Chlamydia pneumoniae in human coronary atherosclerotic plaques Heart, April 1, 2005; 91(4): 521 - 525. [Abstract] [Full Text] [PDF]

				N. P. Kadoglou, S. S. Daskalopoulou, D. Perrea, and C. D. Liapis Matrix Metalloproteinases and Diabetic Vascular Complications Angiology, March 1, 2005; 56(2): 173 - 189. [Abstract] [PDF]

				A. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]

				T. Tazaki, K. Minoguchi, T. Yokoe, K. T. R. Samson, H. Minoguchi, A. Tanaka, Y. Watanabe, and M. Adachi Increased Levels and Activity of Matrix Metalloproteinase-9 in Obstructive Sleep Apnea Syndrome Am. J. Respir. Crit. Care Med., December 15, 2004; 170(12): 1354 - 1359. [Abstract] [Full Text] [PDF]

				S. M. Lessner, D. E. Martinson, and Z. S. Galis Compensatory Vascular Remodeling During Atherosclerotic Lesion Growth Depends on Matrix Metalloproteinase-9 Activity Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2123 - 2129. [Abstract] [Full Text] [PDF]

				M. H. Tayebjee, G. Y.H. Lip, and R. J. MacFadyen The Unifying Role of Matrix Metalloproteinases in Atheroma and Vascular Stroke Stroke, October 1, 2004; 35(10): 2239 - 2239. [Full Text] [PDF]

				T. L. Medley, T. J. Cole, A. M. Dart, C. D. Gatzka, and B. A. Kingwell Matrix Metalloproteinase-9 Genotype Influences Large Artery Stiffness Through Effects on Aortic Gene and Protein Expression Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1479 - 1484. [Abstract] [Full Text] [PDF]

				Z. S. Galis Vulnerable Plaque: The Devil Is in the Details Circulation, July 20, 2004; 110(3): 244 - 246. [Full Text] [PDF]

				K.J. Molloy, M.M. Thompson, J.L. Jones, E.C. Schwalbe, P.R.F. Bell, A.R. Naylor, and I.M. Loftus Unstable Carotid Plaques Exhibit Raised Matrix Metalloproteinase-8 Activity Circulation, July 20, 2004; 110(3): 337 - 343. [Abstract] [Full Text] [PDF]

				A. R. Morgan, K. Rerkasem, P. J. Gallagher, B. Zhang, G. E. Morris, P. C. Calder, R. F. Grimble, P. Eriksson, W. L. McPheat, C. P. Shearman, et al. Differences in Matrix Metalloproteinase-1 and Matrix Metalloproteinase-12 Transcript Levels Among Carotid Atherosclerotic Plaques With Different Histopathological Characteristics Stroke, June 1, 2004; 35(6): 1310 - 1315. [Abstract] [Full Text] [PDF]

				D. L. Brown, K. K. Desai, B. A. Vakili, C. Nouneh, H.-M. Lee, and L. M. Golub Clinical and Biochemical Results of the Metalloproteinase Inhibition with Subantimicrobial Doses of Doxycycline to Prevent Acute Coronary Syndromes (MIDAS) Pilot Trial Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 733 - 738. [Abstract] [Full Text] [PDF]

				N. S. Haque, J. T. Fallon, J. J. Pan, M. B. Taubman, and P. C. Harpel Chemokine receptor-8 (CCR8) mediates human vascular smooth muscle cell chemotaxis and metalloproteinase-2 secretion Blood, February 15, 2004; 103(4): 1296 - 1304. [Abstract] [Full Text] [PDF]

				K. Kameda, T. Matsunaga, N. Abe, H. Hanada, H. Ishizaka, H. Ono, M. Saitoh, K. Fukui, I. Fukuda, T. Osanai, et al. Correlation of oxidative stress with activity of matrix metalloproteinase in patients with coronary artery disease: Possible role for left ventricular remodelling Eur. Heart J., December 2, 2003; 24(24): 2180 - 2185. [Abstract] [Full Text] [PDF]

				C. B Jones, D. C Sane, and D. M Herrington Matrix metalloproteinases: A review of their structure and role in acute coronary syndrome Cardiovasc Res, October 1, 2003; 59(4): 812 - 823. [Abstract] [Full Text] [PDF]

				R. Magid, T. J. Murphy, and Z. S. Galis Expression of Matrix Metalloproteinase-9 in Endothelial Cells Is Differentially Regulated by Shear Stress: ROLE OF c-Myc J. Biol. Chem., August 29, 2003; 278(35): 32994 - 32999. [Abstract] [Full Text] [PDF]

				R. S. Hundal, A. Gomez-Munoz, J. Y. Kong, B. S. Salh, A. Marotta, V. Duronio, and U. P. Steinbrecher Oxidized Low Density Lipoprotein Inhibits Macrophage Apoptosis by Blocking Ceramide Generation, Thereby Maintaining Protein Kinase B Activation and Bcl-XL Levels J. Biol. Chem., June 27, 2003; 278(27): 24399 - 24408. [Abstract] [Full Text] [PDF]

				K. Asanuma, R. Magid, C. Johnson, R. M. Nerem, and Z. S. Galis Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1778 - H1784. [Abstract] [Full Text] [PDF]

				T. Nagata, H. Kai, R. Shibata, M. Koga, A. Yoshimura, and T. Imaizumi Oncostatin M, an Interleukin-6 Family Cytokine, Upregulates Matrix Metalloproteinase-9 Through the Mitogen-Activated Protein Kinase Kinase-Extracellular Signal-Regulated Kinase Pathway in Cultured Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 588 - 593. [Abstract] [Full Text] [PDF]

				S. Blankenberg, H. J. Rupprecht, O. Poirier, C. Bickel, M. Smieja, G. Hafner, J. Meyer, F. Cambien, L. Tiret, and for the AtheroGene Investigators Plasma Concentrations and Genetic Variation of Matrix Metalloproteinase 9 and Prognosis of Patients With Cardiovascular Disease Circulation, April 1, 2003; 107(12): 1579 - 1585. [Abstract] [Full Text] [PDF]

				A. Castrillo, S. B. Joseph, C. Marathe, D. J. Mangelsdorf, and P. Tontonoz Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages J. Biol. Chem., March 14, 2003; 278(12): 10443 - 10449. [Abstract] [Full Text] [PDF]

				P. K. Chua, M. E. Melish, Q. Yu, R. Yanagihara, K. S. Yamamoto, and V. R. Nerurkar Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease Clin. Vaccine Immunol., March 1, 2003; 10(2): 308 - 314. [Abstract] [Full Text] [PDF]

				P. K. Shah Mechanisms of plaque vulnerability and rupture J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 15S - 22S. [Abstract] [Full Text] [PDF]

				K. Morishige, H. Shimokawa, Y. Matsumoto, Y. Eto, T. Uwatoku, K. Abe, K. Sueishi, and A. Takeshita Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo Cardiovasc Res, February 1, 2003; 57(2): 572 - 585. [Abstract] [Full Text] [PDF]

				M. A. Hernandez-Presa, M. Ortego, J. Tunon, J. L. Martin-Ventura, S. Mas, L. M. Blanco-Colio, C. Aparicio, L. Ortega, J. Gomez-Gerique, F. Vivanco, et al. Simvastatin reduces NF-{kappa}B activity in peripheral mononuclear and in plaque cells of rabbit atheroma more markedly than lipid lowering diet Cardiovasc Res, January 1, 2003; 57(1): 168 - 177. [Abstract] [Full Text] [PDF]

				J. S. Forrester Prevention of Plaque Rupture: A New Paradigm of Therapy Ann Intern Med, November 19, 2002; 137(10): 823 - 833. [Abstract] [Full Text] [PDF]

				Z. S. Galis, C. Johnson, D. Godin, R. Magid, J. M. Shipley, R. M. Senior, and E. Ivan Targeted Disruption of the Matrix Metalloproteinase-9 Gene Impairs Smooth Muscle Cell Migration and Geometrical Arterial Remodeling Circ. Res., November 1, 2002; 91(9): 852 - 859. [Abstract] [Full Text] [PDF]

				Y. Gidron, H. Gilutz, R. Berger, and M. Huleihel Molecular and cellular interface between behavior and acute coronary syndromes Cardiovasc Res, October 1, 2002; 56(1): 15 - 21. [Abstract] [Full Text] [PDF]

				P. Verhamme, R. Quarck, H. Hao, M. Knaapen, S. Dymarkowski, H. Bernar, J. Van Cleemput, S. Janssens, J. Vermylen, G. Gabbiani, et al. Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs Cardiovasc Res, October 1, 2002; 56(1): 135 - 144. [Abstract] [Full Text] [PDF]

				A. Maehara, G. S. Mintz, A. B. Bui, O. R. Walter, M. T. Castagna, D. Canos, A. D. Pichard, L. F. Satler, R. Waksman, W. O. Suddath, et al. Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound J. Am. Coll. Cardiol., September 4, 2002; 40(5): 904 - 910. [Abstract] [Full Text] [PDF]

				I. Loftus and M. Thompson The role of matrix metalloproteinases in vascular disease Vascular Medicine, May 1, 2002; 7(2): 117 - 133. [Abstract] [PDF]

				Z. S. Galis and J. J. Khatri Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: The Good, the Bad, and the Ugly Circ. Res., February 22, 2002; 90(3): 251 - 262. [Abstract] [Full Text] [PDF]

				P. K. Shah and Z. S. Galis Matrix Metalloproteinase Hypothesis of Plaque Rupture: Players Keep Piling Up But Questions Remain Circulation, October 16, 2001; 104(16): 1878 - 1880. [Full Text] [PDF]

				M. P. Herman, G. K. Sukhova, P. Libby, N. Gerdes, N. Tang, D. B. Horton, M. Kilbride, R. E. Breitbart, M. Chun, and U. Schonbeck Expression of Neutrophil Collagenase (Matrix Metalloproteinase-8) in Human Atheroma: A Novel Collagenolytic Pathway Suggested by Transcriptional Profiling Circulation, October 16, 2001; 104(16): 1899 - 1904. [Abstract] [Full Text] [PDF]

				P. J. Pollanen, P. J. Karhunen, J. Mikkelsson, P. Laippala, M. Perola, A. Penttila, K. M. Mattila, T. Koivula, and T. Lehtimaki Coronary Artery Complicated Lesion Area Is Related to Functional Polymorphism of Matrix Metalloproteinase 9 Gene: An Autopsy Study Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1446 - 1450. [Abstract] [Full Text] [PDF]

				M. Aikawa and P. Libby Vascular inflammation and activation: new targets for lipid lowering Eur. Heart J. Suppl., May 1, 2001; 3(suppl_B): B3 - B11. [Abstract] [PDF]

				S. Bellosta, M. Canavesi, E. Favari, L. Cominacini, G. Gaviraghi, R. Fumagalli, R. Paoletti, and F. Bernini Lalsoacidipine Modulates the Secretion of Matrix Metalloproteinase-9 by Human Macrophages J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 736 - 743. [Abstract] [Full Text]

				S. Sugiyama, Y. Okada, G. K. Sukhova, R. Virmani, J. W. Heinecke, and P. Libby Macrophage Myeloperoxidase Regulation by Granulocyte Macrophage Colony-Stimulating Factor in Human Atherosclerosis and Implications in Acute Coronary Syndromes Am. J. Pathol., March 1, 2001; 158(3): 879 - 891. [Abstract] [Full Text] [PDF]

				E. Mostafa Mtairag, S. Chollet-Martin, M. Oudghiri, N. Laquay, M.-P. Jacob, J.-B. Michel, and L. J. Feldman Effects of interleukin-10 on monocyte/endothelial cell adhesion and MMP-9/TIMP-1 secretion Cardiovasc Res, March 1, 2001; 49(4): 882 - 890. [Abstract] [Full Text] [PDF]

				P. Vehmaan-Kreula, M. Puolakkainen, M. Sarvas, H. G. Welgus, and P. T. Kovanen Chlamydia pneumoniae Proteins Induce Secretion of the 92-kDa Gelatinase by Human Monocyte- Derived Macrophages Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21 (1): e1 - e8. [Abstract] [Full Text] [PDF]

				R.R Azar, S Rinfret, P Theroux, P.H Stone, R Dakshinamurthy, Y.-J Feng, A.H.B Wu, G Range, and D.D Waters A randomized placebo-controlled trial to assess the efficacy of antiinflammatory therapy with methylprednisolone in unstable angina (MUNA trial) Eur. Heart J., December 2, 2000; 21(24): 2026 - 2032. [Abstract] [PDF]

				D. Zanger, B. K. Yang, J. Ardans, M. A. Waclawiw, G. Csako, L. M. Wahl, and R. O. Cannon III Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1797 - 1802. [Abstract] [Full Text] [PDF]

				P.-P. H. Lee, J.-J. Hwang, G. Murphy, and M. M. Ip Functional Significance of MMP-9 in Tumor Necrosis Factor-Induced Proliferation and Branching Morphogenesis of Mammary Epithelial Cells Endocrinology, October 1, 2000; 141(10): 3764 - 3773. [Abstract] [Full Text] [PDF]

				S. Jormsjo, S. Ye, J. Moritz, D. H. Walter, S. Dimmeler, A. M. Zeiher, A. Henney, A. Hamsten, and P. Eriksson Allele-Specific Regulation of Matrix Metalloproteinase-12 Gene Activity Is Associated With Coronary Artery Luminal Dimensions in Diabetic Patients With Manifest Coronary Artery Disease Circ. Res., May 12, 2000; 86(9): 998 - 1003. [Abstract] [Full Text] [PDF]

				P. WEXBERG and M. GOTTSAUNER-WOLF Intravascular radiotherapy: restenosis and more? Heart, May 1, 2000; 83(5): 497 - 498. [Full Text]