Role of Matrix Metalloproteinases and Aortic Wall Degradation in Abdominal Aortic Aneurysms

  • George A. AntoniouEmail author
  • George S. Georgiadis


AAA is the most common type of true aneurysm. Aneurysm is defined as local dilatation of at least 1.5 times the expected normal arterial diameter. In clinical practice, a practical definition for AAA of a transverse diameter of greater than 3 cm is used. It is present in 5–10 % of men aged between 65 and 79 years [1]. Its major complication is rupture, which presents as a surgical emergency. The mortality associated with rupture is high; approximately 80 % of those who reach the hospital and 50 % of those undergoing emergency surgery for ruptured AAA will die [2]. In the United States, ruptured AAA is the 15th leading cause of death overall [3]. Elective aneurysm repair is associated with a 30-day mortality of 2–6 % [4]. These mortality figures have not changed in the last decades, despite improvements in operative techniques and perioperative management. Furthermore, the incidence of AAA seems to be increasing, which cannot be explained only by improvements in detection [5].


Aortic Aneurysm Abdominal Aortic Aneurysm Abdominal Aortic Aneurysm Aortic Wall Aneurysm Development 
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  1. 1.
    Vardulaki KA, Prevost TC, Walker NM, Day NE, Wilmink AB, Quick CR, et al. Incidence among men of asymptomatic abdominal aortic aneurysms: estimates from 500 screen detected cases. J Med Screen. 1999;6(1):50–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Basnyat PS, Biffin AH, Moseley LG, Hedges AR, Lewis MH. Mortality from ruptured abdominal aortic aneurysm in Wales. Br J Surg. 1999;86(6):765–70.PubMedCrossRefGoogle Scholar
  3. 3.
    Silverberg E, Boring CC, Squires TS. Cancer statistics, 1990. CA Cancer J Clin. 1990;40(1):9–26.PubMedCrossRefGoogle Scholar
  4. 4.
    Huber TS, Wang JG, Derrow AE, Dame DA, Ozaki CK, Zelenock GB, et al. Experience in the United States with intact abdominal aortic aneurysm repair. J Vasc Surg. 2001;33(2):304–10, discussion 310–1.PubMedCrossRefGoogle Scholar
  5. 5.
    Sakalihasan N, Limet R, Defawe OD. Abdominal aortic aneurysm. Lancet. 2005;365(9470):1577–89.PubMedCrossRefGoogle Scholar
  6. 6.
    Ailawadi G, Eliason JL, Upchurch Jr GR. Current concepts in the pathogenesis of abdominal aortic aneurysm. J Vasc Surg. 2003;38(3):584–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Wassef M, Baxter BT, Chisholm RL, Dalman RL, Fillinger MF, Heinecke J, et al. Pathogenesis of abdominal aortic aneurysms: a multidisciplinary research program supported by the National Heart, Lung, and Blood Institute. J Vasc Surg. 2001;34(4):730–8.PubMedCrossRefGoogle Scholar
  8. 8.
    White JV, Haas K, Phillips S, Comerota AJ. Adventitial elastolysis is a primary event in aneurysm formation. J Vasc Surg. 1993;17(2):371–80.PubMedCrossRefGoogle Scholar
  9. 9.
    Krettek A, Sukhova GK, Libby P. Elastogenesis in human arterial disease: a role for macrophages in disordered elastin synthesis. Arterioscler Thromb Vasc Biol. 2003;23(4):582–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Rucker RB, Tinker D. Structure and metabolism of arterial elastin. Int Rev Exp Pathol. 1977;17:1–47.PubMedGoogle Scholar
  11. 11.
    Rizzo RJ, McCarthy WJ, Dixit SN, Lilly MP, Shively VP, Flinn WR, et al. Collagen types and matrix protein content in human abdominal aortic aneurysms. J Vasc Surg. 1989;10(4):365–73.PubMedGoogle Scholar
  12. 12.
    Busuttil RW, Abou-Zamzam AM, Machleder HI. Collagenase activity of the human aorta. A comparison of patients with and without abdominal aortic aneurysms. Arch Surg. 1980;115(11):1373–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Campa JS, Greenhalgh RM, Powell JT. Elastin degradation in abdominal aortic aneurysms. Atherosclerosis. 1987;65(1–2):13–21.PubMedCrossRefGoogle Scholar
  14. 14.
    Keeling WB, Armstrong PA, Stone PA, Bandyk DF, Shames ML. An overview of matrix metalloproteinases in the pathogenesis and treatment of abdominal aortic aneurysms. Vasc Endovascular Surg. 2005;39(6):457–64.PubMedCrossRefGoogle Scholar
  15. 15.
    Pearce WH, Shively VP. Abdominal aortic aneurysm as a complex multifactorial disease: interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs. Ann N Y Acad Sci. 2006;1085:117–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM, Powell JT. Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 1995;15(8):1145–51.PubMedCrossRefGoogle Scholar
  17. 17.
    McMillan WD, Tamarina NA, Cipollone M, Johnson DA, Parker MA, Pearce WH. Size matters: the relationship between MMP-9 expression and aortic diameter. Circulation. 1997;96(7):2228–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Thompson M, Cockerill G. Matrix metalloproteinase-2: the forgotten enzyme in aneurysm pathogenesis. Ann N Y Acad Sci. 2006;1085:170–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Petersen E, Gineitis A, Wågberg F, Angquist KA. Activity of matrix metalloproteinase-2 and −9 in abdominal aortic aneurysms. Relation to size and rupture. Eur J Vasc Endovasc Surg. 2000;20(5):457–61.PubMedCrossRefGoogle Scholar
  20. 20.
    Schönbeck U, Sukhova GK, Gerdes N, Libby P. T(H)2 ­predominant immune responses prevail in human abdominal aortic aneurysm. Am J Pathol. 2002;161(2):499–506.PubMedCrossRefGoogle Scholar
  21. 21.
    Lindholt JS, Shi GP. Chronic inflammation, immune response, and infection in abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2006;31(5):453–63.PubMedCrossRefGoogle Scholar
  22. 22.
    Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2006;26(5):987–94.PubMedCrossRefGoogle Scholar
  23. 23.
    Zhang J, Schmidt J, Ryschich E, Mueller-Schilling M, Schumacher H, Allenberg JR. Inducible nitric oxide synthase is present in human abdominal aortic aneurysm and promotes oxidative vascular injury. J Vasc Surg. 2003;38(2):360–7.PubMedCrossRefGoogle Scholar
  24. 24.
    McCormick ML, Gavrila D, Weintraub NL. Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2007;27(3):461–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Curci JA. Digging in the “soil” of the aorta to understand the growth of abdominal aortic aneurysms. Vascular. 2009;17 Suppl 1:S21–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Curci JA, Thompson RW. Adaptive cellular immunity in aortic aneurysms: cause, consequence, or context? J Clin Invest. 2004;114(2):168–71.PubMedGoogle Scholar
  27. 27.
    Zucker S, Cao J, Chen WT. Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment. Oncogene. 2000;19(56):6642–50.PubMedCrossRefGoogle Scholar
  28. 28.
    Hanemaaijer R, Visser H, Koolwijk P, Sorsa T, Salo T, Golub LM, et al. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv Dent Res. 1998;12(2):114–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Baxter BT, Pearce WH, Waltke EA, Littooy FN, Hallett Jr JW, Kent KC, et al. Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study. J Vasc Surg. 2002;36(1):1–12.PubMedCrossRefGoogle Scholar
  30. 30.
    Aziz F, Kuivaniemi H. Role of matrix metalloproteinase inhibitors in preventing abdominal aortic aneurysm. Ann Vasc Surg. 2007;21(3):392–401.PubMedCrossRefGoogle Scholar
  31. 31.
    Salo JA, Soisalon-Soininen S, Bondestam S, Mattila PS. Familial occurrence of abdominal aortic aneurysm. Ann Intern Med. 1999;130(8):637–42.PubMedCrossRefGoogle Scholar
  32. 32.
    Baird PA, Sadovnick AD, Yee IM, Cole CW, Cole L. Sibling risks of abdominal aortic aneurysm. Lancet. 1995;346(8975):601–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Sandford RM, Bown MJ, London NJ, Sayers RD. The genetic basis of abdominal aortic aneurysms: a review. Eur J Vasc Endovasc Surg. 2007;33(4):381–90.PubMedCrossRefGoogle Scholar
  34. 34.
    Thompson AR, Drenos F, Hafez H, Humphries SE. Candidate gene association studies in abdominal aortic aneurysm disease: a review and meta-analysis. Eur J Vasc Endovasc Surg. 2008;35(1):19–30.PubMedCrossRefGoogle Scholar
  35. 35.
    Kontusaari S, Tromp G, Kuivaniemi H, Ladda RL, Prockop DJ. Inheritance of an RNA splicing mutation (G  +  1 IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV. Am J Hum Genet. 1990;47(1):112–20.PubMedGoogle Scholar
  36. 36.
    Gott VL, Laschinger JC, Cameron DE, Dietz HC, Greene PS, Gillinov AM, et al. The Marfan syndrome and the cardiovascular surgeon. Eur J Cardiothorac Surg. 1996;10(3):149–58.PubMedCrossRefGoogle Scholar

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© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of Vascular and Endovascular SurgeryManchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation TrustManchesterUK
  2. 2.Department of Vascular and Endovascular SurgeryUniversity Hospital of Alexandroupolis, Democritus University of ThraceAlexandroupolisGreece

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