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Expression of ADAMTS-2, -3, -13, and -14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina

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Abstract

ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) proteases are emerging as key participants in the pathogenesis of vascular diseases. We studied the expression of ADAMTS-2, -3, -4 and -14 in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Tissue samples were gathered from 52 patients with AMI (n = 35) or stable angina (n = 17) who underwent directional coronary atherectomy. The specimens were stained with hematoxylin-eosin and analyzed immunohistochemically using antibodies specific to ADAMTS-2, -3, -13 and -14, and markers for endothelial cells, macrophages, and smooth muscle cells. Baseline characteristics of the groups were mostly similar. The proportion of smooth muscle α-actin-immunopositive area was smaller in the AMI group than in the stable angina group, but the areas immunopositive for CD31 or CD68 were higher in the AMI group. The relative areas immunopositive for ADAMTS-2, -3, and -13 in AMI were significantly larger than those in stable angina. However, the proportion of areas immunopositive for ADAMTS-14 did not differ between the two groups. Areas that stained for ADAMTS-2, -3, -13, and -14 largely overlapped with those positive for CD31 or CD68. The areas immunopositive for ADAMTS proteases were significantly correlated with CD31- or CD68-immunostained areas. In conclusions, ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina. These results support a role for these enzymes in the pathogenesis of AMI.

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References

  1. Libby P (1995) Molecular bases of the acute coronary syndromes. Circulation 91:2844–2850

    PubMed  CAS  Google Scholar 

  2. Burke AP, Kolodgie FD, Farb A, Weber DK, Malcom GT, Smialek J, Virmani R (2001) Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circulation 103:934–940

    PubMed  CAS  Google Scholar 

  3. Porter S, Clark IM, Kevorkian L, Edwards DR (2005) The ADAMTS metalloproteinases. Biochem J 386:15–27

    Article  PubMed  CAS  Google Scholar 

  4. Salter RC, Ashlin TG, Kwan AP, Ramji DP (2010) ADAMTS proteases: Key roles in atherosclerosis? J Mol Med 88:1203–1211

    Article  PubMed  CAS  Google Scholar 

  5. Hofer T, Frankenburger M, Mages J, Lang R, Hoffmann R, Colige A, Ziegler-Heitbrock L (2008) Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids. J Mol Med 86:323–332

    Article  PubMed  CAS  Google Scholar 

  6. Colige A, van den Berghe I, Thiry M, Lambert CA, van Beeumen J, Li SW et al (2002) Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3. J Biol Chem 277:5756–5766

    Article  PubMed  CAS  Google Scholar 

  7. Nelson F, Dahlberg L, Laverty S, Reiner A, Pidoux I, Ionescu M et al (1998) Evidence for altered synthesis of type II collagen in patients with osteoarthritis. J Clin Invest 102:2115–2125

    Article  PubMed  CAS  Google Scholar 

  8. Fujikawa K, Suzuki H, McMullen B, Chung D (2001) Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 98:1662–1666

    Article  PubMed  CAS  Google Scholar 

  9. Long Zheng X (2010) ADAMTS13 testing: Why bother? Blood 115:1475–1476

    Article  PubMed  Google Scholar 

  10. Moriguchi-Goto S, Yamashita A, Tamura N, Soejima K, Takahashi M, Nakagaki T, Goto S, Asada Y (2009) ADAMTS-13 attenuates thrombus formation on type I collagen surface and disrupted plaques under flow conditions. Atherosclerosis 203:409–416

    Article  PubMed  CAS  Google Scholar 

  11. Kurisu S, Sato H, Tateishi H, Kawagoe T, Ishihara M, Shimatani Y, Sakai K, Ueda K, Matsuura H (1997) Directional coronary atherectomy for the treatment of acute myocardial infarction. Am Heart J 134:345–350

    Article  PubMed  CAS  Google Scholar 

  12. McKnight J, Studeny M, Roberts G, Touchon R, Wehner P (2001) Directional coronary atherectomy in acute myocardial infarction. W V Med J 97:109–110

    PubMed  CAS  Google Scholar 

  13. Rioufol G, Finet G, Ginon I, André-Fouët X, Rossi R, Vialle E, Desjoyaux E, Convert G, Huret JF, Tabib A (2002) Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 106:804–808

    Article  PubMed  CAS  Google Scholar 

  14. Hong MK, Mintz GS, Lee CW, Suh IW, Hwang ES, Jeong YH, Park DW, Kim YH, Han KH, Cheong SS, Kim JJ, Park SW, Park SJ (2007) Serial intravascular ultrasound evidence of both plaque stabilization and lesion progression in patients with ruptured coronary plaques: effects of statin therapy on ruptured coronary plaque. Atherosclerosis 191:107–114

    Article  PubMed  CAS  Google Scholar 

  15. Colige A, Beschin A, Samyn B, Goebels Y, Van Beeumen J, Nusgens BV, Lapiere CM (1995) Characterization and partial amino acid sequencing of a 107-kDa procollagen I N-proteinase purified by affinity chromatography on immobilized type XIV collagen. J Biol Chem 270:16724–16730

    Article  PubMed  CAS  Google Scholar 

  16. Colige A, Li SW, Sieron AL, Nusgens BV, Prockop DJ, Lapiere CM (1997) cDNA cloning and expression of bovine procollagen I N-proteinase: a new member of the superfamily of zinc-metalloproteinases with binding sites for cells and other matrix components. Proc Natl Acad Sci USA 94:2374–2379

    Article  PubMed  CAS  Google Scholar 

  17. Fernandes RJ, Hirohata S, Engle JM, Colige A, Cohn DH, Eyre DR, Apte SS (2001) Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis. J Biol Chem 276:31502–31509

    Article  PubMed  CAS  Google Scholar 

  18. Wang WM, Lee S, Steiglitz BM, Scott IC, Lebares CC, Allen ML, Brenner MC, Takahara K, Greenspan DS (2003) Transforming growth factor-beta induces secretion of activated ADAMTS-2. A procollagen III N-proteinase. J Biol Chem 278:19549–19557

    Article  PubMed  CAS  Google Scholar 

  19. Rekhter MD (1999) Collagen synthesis in atherosclerosis: too much and not enough. Cardiovasc Res 41:376–384

    Article  PubMed  CAS  Google Scholar 

  20. Braunwald E (1990) Coronary artery patency in patients with myocardial infarction. J Am Coll Cardiol 16:1550–1552

    Article  PubMed  CAS  Google Scholar 

  21. Soejima K, Mimura N, Hirashima M, Maeda H, Hamamoto T, Nakagaki T, Nozaki C (2001) A novel human metalloprotease synthesized in the liver and secreted into the blood: Possibly, the von Willebrand factor-cleaving protease? J Biochem 130:475–480

    Article  PubMed  CAS  Google Scholar 

  22. Sadler JE (1998) Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 67:395–424

    Article  PubMed  CAS  Google Scholar 

  23. Turner N, Nolasco L, Tao Z, Dong JF, Moake J (2006) Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost 4:1396–1404

    Article  PubMed  CAS  Google Scholar 

  24. Levy GG, Motto DG, Ginsburg D (2005) ADAMTS13 turns 3. Blood 106:11–17

    Article  PubMed  CAS  Google Scholar 

  25. Rittersma SZ, van der Wal AC, Koch KT, Piek JJ, Henriques JP, Mulder KJ, Ploegmakers JP, Meesterman M, de Winter RJ (2005) Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: a pathological thrombectomy study in primary percutaneous coronary intervention. Circulation 111:1160–1165

    Article  PubMed  Google Scholar 

  26. Kramer MC, Rittersma SZ, de Winter RJ, Ladich ER, Fowler DR, Liang YH, Kutys R, Carter-Monroe N, Kolodgie FD, van der Wal AC, Virmani R (2010) Relationship of thrombus healing to underlying plaque morphology in sudden coronary death. J Am Coll Cardiol 55:122–132

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A090264).

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None.

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Authors and Affiliations

  1. Department of Medicine, University of Ulsan, Seoul, Korea

    Cheol Whan Lee, Duk-Woo Park, Su-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Seong-Wook Park & Seung-Jung Park

  2. Department of Pathology, School of Medicine, Keimyung University, 194 Dongsan-Dong, Choong-Ku, Daegu, Korea

    Ilseon Hwang

  3. Department of Pathology, Asan Medical Center, University of Ulsan, Seoul, Korea

    Chan-Sik Park

  4. Asan Institute of Life Science, University of Ulsan, Seoul, Korea

    Hyangsin Lee

  5. Division of Cardiology, Asan Medical Center, University of Ulsan, 388-1 Pungnap-dong, Songpa-gu, Seoul, 138-736, Korea

    Seung-Jung Park

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  1. Cheol Whan Lee
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Corresponding author

Correspondence to Seung-Jung Park.

Additional information

Cheol Whan Lee and Ilseon Hwang contributed equally to this article.

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Lee, C.W., Hwang, I., Park, CS. et al. Expression of ADAMTS-2, -3, -13, and -14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina. J Thromb Thrombolysis 33, 362–370 (2012). https://doi.org/10.1007/s11239-011-0673-7

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  • DOI: https://doi.org/10.1007/s11239-011-0673-7

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