Etiology of aortic dissection

  • Koichi AkutsuEmail author
Current Topics Review Article


We discuss the etiology of aortic dissection (AD) from various points of view. The development of AD requires two pathological conditions: medial degeneration and mechanical wall stress. First, histopathological findings of medial degeneration are hypothesized to be due to a loss of elastic fibers and interconnecting elastic fibers. Damage to the vasa vasorum plays a key role in creating an entry site. The clinical causes of medial degeneration include hypertension, aortic aneurysms, obstructive sleep apnea, and connective tissue disorders. Second, mechanical wall stress is supposedly induced by shear stress caused by blood flow, together with hypertension and aortic root movement. Further investigation is necessary in the search for mechanisms responsible for medial degeneration prior to AD development.


Aortic dissection Etiology Medial degeneration Shear wall stress Connective tissue disorder Vasa vasorum 


Compliance with ethical standards

Conflict of interest

The author declares no competing financial interests.


  1. 1.
    Hirst AE Jr, Johns VJ Jr, KIime SW Jr. Dissecting aneurysm of the aorta: a review of 505 cases. Medicine (Baltimore). 1958;37:217–79.CrossRefGoogle Scholar
  2. 2.
    Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL, et al. The international registry of acute aortic dissection (IRAD): new insights into an old disease. JAMA. 2000;283:897–903.CrossRefGoogle Scholar
  3. 3.
    Nienaber CA, Fattori R, Mehta RH, Richartz BM, Evangelista A, Petzsch M, et al. International registry of acute aortic dissection. Gender-related differences in acute aortic dissection. Circulation. 2004;109:3014–21.CrossRefGoogle Scholar
  4. 4.
    Halushka MK, Angelini A, Bartoloni G, Basso C, Batoroeva L, Bruneval P, et al. Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: II. Noninflammatory degenerative diseases—nomenclature and diagnostic criteria. Cardiovasc Pathol. 2016;25:247–57.CrossRefGoogle Scholar
  5. 5.
    Wilson SK, Hutchins GM. Aortic dissecting aneurysms: causative factors in 204 subjects. Arch Pathol Lab Med. 1982;106:175–80.Google Scholar
  6. 6.
    Larson EW, Edwards WD. Risk factors for aortic dissection: a necropsy study of 161 cases. Am J Cardiol. 1984;53:849–55.CrossRefGoogle Scholar
  7. 7.
    Nakashima Y, Kurozumi T, Sueishi K, Tanaka K. Dissecting aneurysm: a clinicopathologic and histopathologic study of 111 autopsied cases. Hum Pathol. 1990;21:291–6.CrossRefGoogle Scholar
  8. 8.
    Carlson RG, Lillehei CW, Edwards JE. Cystic medial necrosis of the ascending aorta in relation to age and hypertension. Am J Cardiol. 1970;25:411–5.CrossRefGoogle Scholar
  9. 9.
    Kageyama N, Ro A, Tanifuji T, Kumagai T, Murai T, Fukunaga T. The histopathologic study of elastic laminar and interconnecting elastic fiber in aortic media: Implications for aortic dissection (Japanese). J Jpn Coll Angiol. 2005;45:1003–9.Google Scholar
  10. 10.
    Roberts WC, Vowels TJ, Kitchens BL, Ko JM, Filardo G, Henry AC, et al. Aortic medial elastic fiber loss in acute ascending aortic dissection. Am J Cardiol. 2011;108:1639–44.CrossRefGoogle Scholar
  11. 11.
    Nakashima Y, Shiokawa Y, Sueishi K. Alterations of elastic architecture in human aortic dissecting aneurysm. Lab Investig. 1990;62:751–60.Google Scholar
  12. 12.
    Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788–98.CrossRefGoogle Scholar
  13. 13.
    Morisaki H, Akutsu K, Ogino H, Kondo N, Yamanaka I, Tsutsumi Y, et al. Mutation of ACTA2 gene as an important cause of familial and non-familial non-syndromatic thoracic aortic aneurysm and/or dissection. Hum Mutat. 2009;30:1406–11.CrossRefGoogle Scholar
  14. 14.
    van de Laar IM, van der Linde D, Oei EH, Bos PK, Bessems JH, Bierma-Zeinstra SM, et al. Phenotypic spectrum of the SMAD3-related aneurysms-osteoarthritis syndrome. J Med Genet. 2012;49:47–57.CrossRefGoogle Scholar
  15. 15.
    Boileau C, Guo DC, Hanna N, Regalado ES, Detaint D, Gong L, et al. TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. Nat Genet. 2012;44:916–21.CrossRefGoogle Scholar
  16. 16.
    Détaint D, Faivre L, Collod-Beroud G, Child AH, Loeys BL, Binquet C, et al. Cardiovascular manifestations in men and women carrying a FBN1 mutation. Eur Heart J. 2010;31:2223–9.CrossRefGoogle Scholar
  17. 17.
    Akutsu K, Morisaki H, Takeshita S, Sakamoto S, Tamori Y, Yoshimuta T, et al. Phenotypic heterogeneity of Marfan-like connective tissue disorders associated with mutations of the transforming growth factor-β receptor gene. Circ J. 2007;71:1305–9.CrossRefGoogle Scholar
  18. 18.
    Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, et al. ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2873–926.CrossRefGoogle Scholar
  19. 19.
    Oderich GS, Panneton JM, Bower TC, Lindor NM, Cherry KJ, Noel AA, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005;42:98–106.CrossRefGoogle Scholar
  20. 20.
    Januzzi JL, Isselbacher EM, Fattori R, Cooper JV, Smith DE, Fang J, et al. Characterizing the young patient with aortic dissection: results from the international registry of aortic dissection (IRAD). Am Coll Cardiol. 2004;43:665–9.CrossRefGoogle Scholar
  21. 21.
    Hahn RT, Roman MJ, Mogtader AH, Devereux RB. Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves. J Am Coll Cardiol. 1992;19:283–8.CrossRefGoogle Scholar
  22. 22.
    Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW. Bicuspid aortic valve is heritable. J Am Coll Cardiol. 2004;44:138–43.CrossRefGoogle Scholar
  23. 23.
    Bonderman D, Gharehbaghi-Schnell E, Wollenek G, Maurer G, Baumgartner H, Lang IM. Mechanisms underlying aortic dilatation in congenital aortic valve malformation. Circulation. 1999;99:2138–43.CrossRefGoogle Scholar
  24. 24.
    Padang R, Bagnall RD, Richmond DR, Bannon PG, Semsarian C. Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease. J Mol Cell Cardiol. 2012;53:277–81.CrossRefGoogle Scholar
  25. 25.
    Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, et al. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437:270–4.CrossRefGoogle Scholar
  26. 26.
    Akutsu K, Morisaki H, Okajima T, Yoshimuta T, Tsusumi Y, Takeshita S, et al. Genetic analysis of young adult patients with aortic disease not fulfilling the diagnostic criteria for Marfan syndrome. Circ J. 2010;74:990–7.CrossRefGoogle Scholar
  27. 27.
    Suzuki T, Isselbacher EM, Nienaber CA, Pyeritz RE, Eagle KA, Tsai TT, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the international registry of acute aortic dissection [IRAD]). Am J Cardiol. 2012;109:122–7.CrossRefGoogle Scholar
  28. 28.
    Li Y, Yang N, Duan W, Liu S, Yu S, Yi D. Acute aortic dissection in China. Am J Cardiol. 2012;110:1056–61.CrossRefGoogle Scholar
  29. 29.
    Howard DP, Banerjee A, Fairhead JF, Perkins J, Silver LE, Rothwell PM, et al. Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study. Circulation. 2013;127:2031–7.CrossRefGoogle Scholar
  30. 30.
    Pape LA, Awais M, EM, Suzuki T, Trimarchi S, Evangelista A, et al. Presentation, diagnosis, and outcomes of acute aortic dissection: 17-year trends from the international registry of acute aortic dissection. J Am Coll Cardiol. 2015;66:350–8.CrossRefGoogle Scholar
  31. 31.
    Angouras D, Sokolis DP, Dosios T, Kostomitsopoulos N, Boudoulas H, Skalkeas G, et al. Effect of impaired vasa vasorum flow on the structure and mechanics of the thoracic aorta: implications for the pathogenesis of aortic dissection. Eur J Cardiothorac Surg. 2000;17:468–73.CrossRefGoogle Scholar
  32. 32.
    Gao F, Guo Z, Sakamoto M, Matsuzawa T. Fluid-structure interaction within a layered aortic arch model. J Biol Phys. 2006;32:435–54.CrossRefGoogle Scholar
  33. 33.
    Sampol G, Romero O, Salas A, Tovar JL, Lloberes P, Sagales T, et al. Obstructive sleep apnea and thoracic aorta dissection. Am J Respir Crit Care Med. 2003;168:1528–31.CrossRefGoogle Scholar
  34. 34.
    Yanagi H, Imoto K, Suzuki SI, Uchida K, Masuda M, Miyashita A. Acute aortic dissection associated with sleep apnea syndrome. Ann Thorac Cardiovasc Surg. 2013;19:456–60.CrossRefGoogle Scholar
  35. 35.
    Teng HI, Huang CC, Chiang CH, Huang PH, Chung CM, Lin SJ, et al. Sleep apnea and risk of aortic dissection: a nonrandomized, pair-matched cohort study. J Chin Med Assoc. 2016;79:422–7.CrossRefGoogle Scholar
  36. 36.
    Tamori Y, Akutsu K, Kasai S, Sakamoto S, Okajima T, Yoshimuta T, et al. Coexistent true aortic aneurysm as a cause of acute aortic dissection. Circ J. 2009;73:822–5.CrossRefGoogle Scholar
  37. 37.
    Miller DV, Isotalo PA, Weyand CM, Edwards WD, Aubry MC, Tazelaar HD. Surgical pathology of noninfectious ascending aortitis: a study of 45 cases with emphasis on an isolated variant. Am J Surg Pathol. 2006;30:1150–8.CrossRefGoogle Scholar
  38. 38.
    Nasiell J, Lindqvist PG. Aortic dissection in pregnancy: the incidence of a life-threatening disease. Eur J Obstet Gynecol Reprod Biol. 2010;149:120–1.CrossRefGoogle Scholar
  39. 39.
    Oskoui R, Lindsay J Jr. Aortic dissection in women < 40 years of age and the unimportance of pregnancy. Am J Cardiol. 1994;73:821–3.CrossRefGoogle Scholar
  40. 40.
    Reilly JM, Savage EB, Brophy CM, Tilson MD. Hydrocortisone rapidly induces aortic rupture in a genetically susceptible mouse. Arch Surg. 1990;125:707–9.CrossRefGoogle Scholar
  41. 41.
    Roberts WC. Aortic dissection: anatomy, consequences, and causes. Am Heart J. 1981;101:195–214.CrossRefGoogle Scholar
  42. 42.
    Creager MA, Jones DW, Easton JD, Halperin JL, Hirsch AT, Matsumoto AH, et al. American Heart Association. Atherosclerotic Vascular Disease Conference. Writing Group V: Medical decision making and therapy. Circulation. 2004;109:2634–42.CrossRefGoogle Scholar
  43. 43.
    Heistad DD, Marcus ML, Law EG, Armstrong ML, Ehrhardt JC, Abboud FM. Regulation of blood flow to the aortic media in dogs. J Clin Investig. 1978;62:133–40.CrossRefGoogle Scholar
  44. 44.
    Osada H, Kyogoku M, Ishidou M, Morishima M, Nakajima H. Aortic dissection in the outer third of the media: what is the role of the vasa vasorum in the triggering process? Eur J Cardiothorac Surg. 2013;43:e82-8.CrossRefGoogle Scholar
  45. 45.
    Beller CJ, Labrosse MR, Thubrikar MJ, Robicsek F. Role of aortic root motion in the pathogenesis of aortic dissection. Circulation. 2004;109:763–9.CrossRefGoogle Scholar
  46. 46.
    Beller CJ, Labrosse MR, Thubrikar MJ, Robicsek F. Finite element modeling of the thoracic aorta: including aortic root motion to evaluate the risk of aortic dissection. J Med Eng Technol. 2008;32:167–70.CrossRefGoogle Scholar
  47. 47.
    Mitsui H, Uchida H, Teramoto S. Correlation between the layer of an intimal tear and the progression of aortic dissection. Acta Med Okayama. 1994;48:93–9.Google Scholar
  48. 48.
    Guidelines for Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection. (JCS 2011)—Digest Version—JCS Joint Working Group.
  49. 49.
    Harris KM, Braverman AC, Eagle KA, Woznicki EM, Pyeritz RE, Myrmel T, et al. Acute aortic intramural hematoma: an analysis from the international registry of acute aortic dissection. Circulation. 2012;126(11 Suppl 1):91–6.CrossRefGoogle Scholar

Copyright information

© The Japanese Association for Thoracic Surgery 2019

Authors and Affiliations

  1. 1.Division of Vascular Medicine, Department of Cardiovascular Surgery, Kawasaki Aortic CenterKawasaki Saiwai HospitalKawasakiJapan

Personalised recommendations