This Article Full Text Full Text (PDF) 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 Carrell, T. W.G. Articles by Smith, A. Search for Related Content PubMed PubMed Citation Articles by Carrell, T. W.G. Articles by Smith, A. Related Collections Gene expression Peripheral vascular disease CV surgery: aortic and vascular disease

(Circulation. 2002;105:477.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Stromelysin-1 (Matrix Metalloproteinase-3) and Tissue Inhibitor of Metalloproteinase-3 Are Overexpressed in the Wall of Abdominal Aortic Aneurysms

Tom W.G. Carrell, MA, FRCS; Kevin G. Burnand, MS, FRCS; Graham M.A. Wells, BSc; John M. Clements, PhD; Alberto Smith, PhD

From the Academic Department of Surgery (T.W.G.C., K.G.B., A.S.), Kings College, London, and British Biotech Pharmaceuticals Ltd (G.M.A.W., J.M.C.), Oxford, UK.

Correspondence to Alberto Smith, Academic Department of Surgery, GKT Medical School, King’s College, St Thomas’ Campus, London SE1 7EH, UK. E-mail alberto.smith{at}kcl.ac.uk

Background— Atherosclerosis is implicated in the pathogenesis of abdominal aortic aneurysm (AAA) but more often causes aortic occlusive disease (AOD). The matrix metalloproteinases (MMPs) degrade extracellular matrix and may play a central role in the pathogenesis of AAA. The aim of this study was to examine differences in the patterns of MMP and MMP inhibitor expression between AAA and AOD.

Methods and Results— The expression of mRNA for 14 MMPs and 4 tissue inhibitors of metalloproteinases (TIMPs) was estimated in samples of aortic wall from 8 patients with AAA and 8 with AOD using the reverse-transcriptase polymerase chain reaction with a synthetic multicompetitor standard. AAA wall expressed significantly more stromelysin-1 (MMP-3) (mean log₁₀ ratio [copy enzyme cDNA/copy GAPDH cDNA], -1.9; range, -3.3 to -0.7) than the AOD wall (mean, 4; range, -5.7 to -2.4), P<0.005. TIMP-3 expression was significantly higher in AAA (mean, -1.7; range, -2.9 to -1.0) than AOD (mean, -3.6; range, -5.7 to -1.8), P<0.01. Expression of 8 other MMPs (1, 2, 7, 9, 11, 12, 14, and 17) was detected and was similar in AAA and AOD. Expression of the remaining 5 MMPs (-8, -10, -13, -15, and -16) was not detected in any of the samples.

Conclusions— Both AAA and AOD walls express similar levels of a wide range of MMPs, including cell membrane–bound MT-MMPs. Stromelysin-1 (MMP-3) and TIMP-3 were, however, over expressed in the AAA samples and may be involved aneurysm pathogenesis. Stromelysin-1 could provide a target for pharmacological inhibition.

Key Words: aneurysm • aorta • arteriosclerosis • metalloproteinases • polymerase chain reaction

This article has been cited by other articles:

				E. Wilton, M. Bland, M. Thompson, and M. Jahangiri Matrix metalloproteinase expression in the ascending aorta and aortic valve Interactive CardioVascular and Thoracic Surgery, February 1, 2008; 7(1): 37 - 40. [Abstract] [Full Text] [PDF]

				J. Deguara, K. G. Burnand, J. Berg, P. Green, C. M. Lewis, G. Chinien, M. Waltham, P. Taylor, R. F. Stern, E. Solomon, et al. An increased frequency of the 5A allele in the promoter region of the MMP3 gene is associated with abdominal aortic aneurysms Hum. Mol. Genet., December 15, 2007; 16(24): 3002 - 3007. [Abstract] [Full Text] [PDF]

				M. Monaco, P. Stassano, L. Di Tommaso, and G. Iannelli Response of plasma matrix metalloproteinases and tissue inhibitor of metalloproteinases to stent-graft surgery for descending thoracic aortic aneurysms. J. Thorac. Cardiovasc. Surg., October 1, 2007; 134(4): 925 - 931. [Abstract] [Full Text] [PDF]

				W. R. W. Wilson, M. Anderton, E. C. Schwalbe, J. L. Jones, P. N. Furness, P. R.F. Bell, and M. M. Thompson Matrix Metalloproteinase-8 and -9 Are Increased at the Site of Abdominal Aortic Aneurysm Rupture Circulation, January 24, 2006; 113(3): 438 - 445. [Abstract] [Full Text] [PDF]

				W. B. Keeling, P. A. Armstrong, P. A. Stone, D. F. Bandyk, and M. L. Shames An Overview of Matrix Metalloproteinases in the Pathogenesis and Treatment of Abdominal Aortic Aneurysms Vascular and Endovascular Surgery, November 1, 2005; 39(6): 457 - 464. [Abstract] [PDF]

				M. Kazi, C. Zhu, J. Roy, G. Paulsson-Berne, A. Hamsten, J. Swedenborg, U. Hedin, and P. Eriksson Difference in Matrix-Degrading Protease Expression and Activity Between Thrombus-Free and Thrombus-Covered Wall of Abdominal Aortic Aneurysm Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1341 - 1346. [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]

				G. Ailawadi, J. L. Eliason, K. J. Roelofs, I. Sinha, K. K. Hannawa, E. P. Kaldjian, G. Lu, P. K. Henke, J. C. Stanley, S. J. Weiss, et al. Gender Differences in Experimental Aortic Aneurysm Formation Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 2116 - 2122. [Abstract] [Full Text] [PDF]

				B.A. Kelly, B.C. Bond, and L. Poston Aortic adaptation to pregnancy: elevated expression of matrix metalloproteinases-2 and -3 in rat gestation Mol. Hum. Reprod., May 1, 2004; 10(5): 331 - 337. [Abstract] [Full Text] [PDF]

				A. Luttun, E. Lutgens, A. Manderveld, K. Maris, D. Collen, P. Carmeliet, and L. Moons Loss of Matrix Metalloproteinase-9 or Matrix Metalloproteinase-12 Protects Apolipoprotein E-Deficient Mice Against Atherosclerotic Media Destruction but Differentially Affects Plaque Growth Circulation, March 23, 2004; 109(11): 1408 - 1414. [Abstract] [Full Text] [PDF]

				J. T. Powell and A. R. Brady Detection, Management, and Prospects for the Medical Treatment of Small Abdominal Aortic Aneurysms Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): 241 - 245. [Abstract] [Full Text]

				O. D Defawe, A. Colige, C. A Lambert, C. Munaut, P. Delvenne, C. M Lapiere, R. Limet, B. V Nusgens, and N. Sakalihasan TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas Cardiovasc Res, October 15, 2003; 60(1): 205 - 213. [Abstract] [Full Text] [PDF]

				W. Shi, M. D. Brown, X. Wang, J. Wong, D. F. Kallmes, A. H. Matsumoto, G. A. Helm, T. A. Drake, and A. J. Lusis Genetic Backgrounds but Not Sizes of Atherosclerotic Lesions Determine Medial Destruction in the Aortic Root of Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1901 - 1906. [Abstract] [Full Text] [PDF]

				T. L. Medley, B. A. Kingwell, C. D. Gatzka, P. Pillay, and T. J. Cole Matrix Metalloproteinase-3 Genotype Contributes to Age-Related Aortic Stiffening Through Modulation of Gene and Protein Expression Circ. Res., June 13, 2003; 92(11): 1254 - 1261. [Abstract] [Full Text] [PDF]

				V. Fontaine, M.-P. Jacob, X. Houard, P. Rossignol, D. Plissonnier, E. Angles-Cano, and J.-B. Michel Involvement of the Mural Thrombus as a Site of Protease Release and Activation in Human Aortic Aneurysms Am. J. Pathol., November 1, 2002; 161(5): 1701 - 1710. [Abstract] [Full Text] [PDF]

				N. Lamblin, C. Bauters, X. Hermant, J.-M. Lablanche, N. Helbecque, and P. Amouyel Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease J. Am. Coll. Cardiol., July 3, 2002; 40(1): 43 - 48. [Abstract] [Full Text] [PDF]

				V. J. Ferrans New Insights Into the World of Matrix Metalloproteinases Circulation, January 29, 2002; 105(4): 405 - 407. [Full Text] [PDF]