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Smooth Muscle Cells and the Formation, Degeneration, and Rupture of Saccular Intracranial Aneurysm Wall—a Review of Current Pathophysiological Knowledge

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Abstract

Subarachnoid hemorrhage or intracerebral hemorrhage caused by rupture of a saccular intracranial aneurysm (sIA) is often fatal and causes significant loss of productive live years in addition to significant mortality. Around 3.5 % of the middle aged otherwise healthy population carries unruptured sIAs. Many sIAs never rupture, and since their prophylactic treatment is associated with risks of morbidity and even mortality, it is paramount to elucidate the biology that leads to sIA rupture in order be able to identify rupture-prone sIAs and to improve current therapies. Smooth muscle cells (SMCs) play a critical role both in the formation of sIAs, as well as in the repair and adaptation of the sIA wall to hemodynamic and proteolytic stress to which it is subjected. Loss of mural SMCs is characteristic to ruptured sIA walls, and experiments in animal models suggest that this loss of mural SMCs is causative to sIA growth and eventual rupture. Genetic factors that impair the function or survival of SMCs may predispose to sIA formation. Local or systemic therapy that increases the number of functioning SMCs in the sIA wall may have a potential to reduce the risk of sIA rupture. This review discusses the mechanisms and cellular interactions that SMCs have in the pathobiology of the sIA wall.

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References

  1. Rinkel GJ, Djibuti M, Algra A, van Gijn J. Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke. 1998;29:251–6.

    Article  CAS  PubMed  Google Scholar 

  2. Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10:626–36.

    Article  PubMed  Google Scholar 

  3. Juvela S, Poussa K, Lehto H, Porras M. Natural history of unruptured intracranial aneurysms: a long-term follow-up study. Stroke. 2013;44:2414–21.

    Article  PubMed  Google Scholar 

  4. UCAS Japan Investigators, Morita A, Kirino T, Hashi K, Aoki N, Fukuhara S, et al. The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med. 2012;366:2474–82.

    Article  PubMed  Google Scholar 

  5. Wermer MJ, van der Schaaf IC, Algra A, Rinkel GJ. Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke. 2007;38:1404–10.

    Article  PubMed  Google Scholar 

  6. Wiebers DO, Whisnant JP, Huston 3rd J, Meissner I, Brown Jr RD, Piepgras DG, et al. International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362:103–10.

    Article  PubMed  Google Scholar 

  7. Bijlenga P, Ebeling C, Jaegersberg M, Summers P, Rogers A, Waterworth A, et al. Risk of rupture of small anterior communicating artery aneurysms is similar to posterior circulation aneurysms. Stroke. 2013;44:3018–26.

    Article  PubMed  Google Scholar 

  8. Vlak MH, Rinkel GJ, Greebe P, Algra A. Risk of rupture of an intracranial aneurysm based on patient characteristics: a case-control study. Stroke. 2013;44:1256–9.

    Article  PubMed  Google Scholar 

  9. Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ. Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol. 2009;8:635–42.

    Article  PubMed  Google Scholar 

  10. Karamanakos PN, von Und Zu Fraunberg M, Bendel S, Huttunen T, Kurki M, Hernesniemi J, et al. Risk factors for three phases of 12-month mortality in 1657 patients from a defined population after acute aneurysmal subarachnoid hemorrhage. World Neurosurg. 2012;78:631–9.

    Article  PubMed  Google Scholar 

  11. Malmivaara K, Juvela S, Hernesniemi J, Lappalainen J, Siironen J. Health-related quality of life and cost-effectiveness of treatment in subarachnoid haemorrhage. Eur J Neurol. 2012;19:1455–61.

    Article  CAS  PubMed  Google Scholar 

  12. Huttunen T, von und zu Fraunberg M, Frösen J, Lehecka M, Tromp G, Helin K, et al. Saccular intracranial aneurysm disease: distribution of site, size, and age suggests different etiologies for aneurysm formation and rupture in 316 familial and 1454 sporadic eastern Finnish patients. Neurosurgery. 2010;66:631–8.

    Article  PubMed  Google Scholar 

  13. Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet. 2005;366:809–17.

    Article  PubMed  Google Scholar 

  14. Naggara ON, Lecler A, Oppenheim C, Meder JF, Raymond J. Endovascular treatment of intracranial unruptured aneurysms: a systematic review of the literature on safety with emphasis on subgroup analyses. Radiology. 2012;263:828–35.

    Article  PubMed  Google Scholar 

  15. Kotowski M, Naggara O, Darsaut TE, Nolet S, Gevry G, Kouznetsov E, et al. Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011. J Neurol Neurosurg Psychiatry. 2013;84:42–8. Review.

    Article  PubMed  Google Scholar 

  16. Koroknay-Pál P, Lehto H, Niemelä M, Kivisaari R, Hernesniemi J. Long-term outcome of 114 children with cerebral aneurysms. J Neurosurg Pediatr. 2012;9:636–45.

    Article  PubMed  Google Scholar 

  17. Hashimoto N, Handa H, Hazama F. Experimentally induced cerebral aneurysms in rats. Surg Neurol. 1978;10:3–8.

    CAS  PubMed  Google Scholar 

  18. Nagata I, Handa H, Hashimoto N, Hazama F. Experimentally induced cerebral aneurysms in rats: Part VI. Hypertension. Surg Neurol. 1980;14:477–9.

    CAS  PubMed  Google Scholar 

  19. Hashimoto N, Kim C, Kikuchi H, Kojima M, Kang Y, Hazama F. Experimental induction of cerebral aneurysms in monkeys. J Neurosurg. 1987;67:903–5.

    Article  CAS  PubMed  Google Scholar 

  20. Hazama F, Kataoka H, Yamada E, Kayembe K, Hashimoto N, Kojima M, et al. Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study. Am J Pathol. 1986;124:399–404.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Kim C, Kikuchi H, Hashimoto N, Kojima M, Kang Y, Hazama F. Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats. Stroke. 1988;19:507–11.

    Article  CAS  PubMed  Google Scholar 

  22. Kondo S, Hashimoto N, Kikuchi H, Hazama F, Nagata I, Kataoka H. Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke. 1998;29:181–8.

    Article  CAS  PubMed  Google Scholar 

  23. Moriwaki T, Takagi Y, Sadamasa N, Aoki T, Nozaki K, Hashimoto N. Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice. Stroke. 2006;37:900–5.

    Article  CAS  PubMed  Google Scholar 

  24. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Morishita R, Hashimoto N. Reduced collagen biosynthesis is the hallmark of cerebral aneurysm: contribution of interleukin-1beta and nuclear factor-kappaB. Arterioscler Thromb Vasc Biol. 2009;29:1080–6.

    Article  CAS  PubMed  Google Scholar 

  25. Aoki T, Kataoka H, Morimoto M, Nozaki K, Hashimoto N. Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats. Stroke. 2007;38:162–9.

    Article  CAS  PubMed  Google Scholar 

  26. Aoki T, Nishimura M, Kataoka H, Ishibashi R, Nozaki K, Miyamoto S. Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS. Lab Invest. 2011;91:619–26.

    Article  CAS  PubMed  Google Scholar 

  27. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Egashira K, Hashimoto N. Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation. Stroke. 2009;40:942–51.

    Article  CAS  PubMed  Google Scholar 

  28. Aoki T, Kataoka H, Nishimura M, Ishibashi R, Morishita R, Miyamoto S. Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of MCP-1 in vascular smooth muscle cells. Gene Ther. 2010;17:1117–23.

    Article  CAS  PubMed  Google Scholar 

  29. Chen S, Feng H, Sherchan P, Klebe D, Zhao G, Sun X, Zhang J, Tang J, Zhang JH. Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog Neurobiol. 2013.

  30. Frösen J, Piippo A, Paetau A, Kangasniemi M, Niemelä M, Hernesniemi J, et al. Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke. 2004;35:2287–93.

    Article  PubMed  Google Scholar 

  31. Meng H, Wang Z, Hoi Y, Gao L, Metaxa E, Swartz DD, et al. Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke. 2007;38:1924–31.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke. 2001;32:485–91.

    Article  CAS  PubMed  Google Scholar 

  33. Tulamo R, Frösen J, Junnikkala S, Paetau A, Pitkäniemi J, Kangasniemi M, et al. Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture. Neurosurgery. 2006;59:1069–76.

    PubMed  Google Scholar 

  34. Coen M, Burkhardt K, Bijlenga P, Gabbiani G, Schaller K, Kövari E, et al. Smooth muscle cells of human intracranial aneurysms assume phenotypic features similar to those of the atherosclerotic plaque. Cardiovasc Pathol. 2013;22:339–44.

    Article  CAS  PubMed  Google Scholar 

  35. Thyberg J. Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury. Histol Histopathol. 1998;13:871–91. Review.

    CAS  PubMed  Google Scholar 

  36. Newby AC, Zaltsman AB. Molecular mechanisms in intimal hyperplasia. J Pathol. 2000;190:300–9. Review.

    Article  CAS  PubMed  Google Scholar 

  37. Abruzzo T, Shengelaia GG, Dawson 3rd RC, Owens DS, Cawley CM, Gravanis MB. Histologic and morphologic comparison of experimental aneurysms with human intracranial aneurysms. AJNR Am J Neuroradiol. 1998;19:1309–14.

    CAS  PubMed  Google Scholar 

  38. Dai D, Ding YH, Danielson MA, Kadirvel R, Lewis DA, Cloft HJ, et al. Histopathologic and immunohistochemical comparison of human, rabbit, and swine aneurysms embolized with platinum coils. AJNR Am J Neuroradiol. 2005;26:2560–8.

    PubMed  Google Scholar 

  39. Bouzeghrane F, Naggara O, Kallmes DF, Berenstein A, Raymond J. International Consortium of Neuroendovascular Centres. In vivo experimental intracranial aneurysm models: a systematic review. AJNR Am J Neuroradiol. 2010;31:418–23. Review.

    Article  CAS  PubMed  Google Scholar 

  40. Frösen J, Marjamaa J, Myllärniemi M, Abo-Ramadan U, Tulamo R, Niemelä M, et al. Contribution of mural and bone marrow-derived neointimal cells to thrombus organization and wall remodeling in a microsurgical murine saccular aneurysm model. Neurosurgery. 2006;58:936–44.

    Article  PubMed  Google Scholar 

  41. Marbacher S, MD, Marjamaa J, MD, Bradacova K, von Gunten M, Honkanen P, Abo-Ramadan U, Hernesniemi J, Niemelä M, Frösen J. Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model. Stroke. In press.

  42. Kataoka K, Taneda M, Asai T, Kinoshita A, Ito M, Kuroda R. Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured and unruptured cerebral aneurysms. Stroke. 1999;30:1396–401.

    Article  CAS  PubMed  Google Scholar 

  43. Frösen J, Tulamo R, Heikura T, Sammalkorpi S, Niemelä M, Hernesniemi J, et al. Lipid accumulation, lipid oxidation, and low plasma levels of acquired antibodies against oxidized lipids associate with degeneration and rupture of the intracranial aneurysm wall. Acta Neuropathol Commun. 2013;1:71.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Hara A, Yoshimi N, Mori H. Evidence for apoptosis in human intracranial aneurysms. Neurol Res. 1998;20:127–30.

    CAS  PubMed  Google Scholar 

  45. Sakaki T, Kohmura E, Kishiguchi T, Yuguchi T, Yamashita T, Hayakawa T. Loss and apoptosis of smooth muscle cells in intracranial aneurysms. Studies with in situ DNA end labeling and antibody against single-stranded DNA. Acta Neurochir (Wien). 1997;139:469–74.

    Article  CAS  Google Scholar 

  46. Pentimalli L, Modesti A, Vignati A, Marchese E, Albanese A, Di Rocco F, et al. Role of apoptosis in intracranial aneurysm rupture. J Neurosurg. 2004;101:1018–25.

    Article  PubMed  Google Scholar 

  47. Laaksamo E, Tulamo R, Liiman A, Baumann M, Friedlander RM, Hernesniemi J, et al. Oxidative stress is associated with cell death, wall degradation, and increased risk of rupture of the intracranial aneurysm wall. Neurosurgery. 2013;72:109–17.

    Article  PubMed  Google Scholar 

  48. Guo F, Li Z, Song L, Han T, Feng Q, Guo Y, et al. Increased apoptosis and cysteinyl aspartate specific protease-3 gene expression in human intracranial aneurysm. J Clin Neurosci. 2007;14:550–5.

    Article  CAS  PubMed  Google Scholar 

  49. Frösen J, Tulamo R, Paetau A, Laaksamo E, Korja M, Laakso A, et al. Saccular intracranial aneurysm: pathology and mechanisms. Acta Neuropathol. 2012;123:773–86.

    Article  PubMed  Google Scholar 

  50. Tulamo R, Frösen J, Junnikkala S, Paetau A, Kangasniemi M, Peláez J, et al. Complement system becomes activated by the classical pathway in intracranial aneurysm walls. Lab Invest. 2010;90:168–79.

    Article  CAS  PubMed  Google Scholar 

  51. Bygglin H, Laaksamo E, Myllärniemi M, Tulamo R, Hernesniemi J, Niemelä M, et al. Isolation, culture, and characterization of smooth muscle cells from human intracranial aneurysms. Acta Neurochir (Wien). 2011;153:311–8.

    Article  Google Scholar 

  52. Krischek B, Inoue I. The genetics of intracranial aneurysms. J Hum Genet. 2006;51:587–94.

    Article  PubMed  Google Scholar 

  53. Ruigrok YM, Rinkel GJ. Genetics of intracranial aneurysms. Stroke. 2008;39:1049–55. Review.

    Article  PubMed  Google Scholar 

  54. Alg VS, Sofat R, Houlden H, Werring DJ. Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals. Neurology. 2013;80:2154–65.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Helgadottir A, Thorleifsson G, Magnusson KP, Grétarsdottir S, Steinthorsdottir V, Manolescu A, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet. 2008;40:217–24.

    Article  CAS  PubMed  Google Scholar 

  56. Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nat Genet. 2010;42:420–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Leeper NJ, Raiesdana A, Kojima Y, Kundu RK, Cheng H, Maegdefessel L, et al. Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation. Arterioscler Thromb Vasc Biol. 2013;33:e1–10. Epub 2012 Nov 15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Roder C, Kasuya H, Harati A, Tatagiba M, Inoue I, Krischek B. Meta-analysis of microarray gene expression studies on intracranial aneurysms. Neuroscience. 2012;201:105–13.

    Article  CAS  PubMed  Google Scholar 

  59. Aoki T, Kataoka H, Ishibashi R, Nozaki K, Hashimoto N. Gene expression profile of the intima and media of experimentally induced cerebral aneurysms in rats by laser-microdissection and microarray techniques. Int J Mol Med. 2008;22:595–603.

    CAS  PubMed  Google Scholar 

  60. Kurki MI, Häkkinen SK, Frösen J, Tulamo R, von und zu Fraunberg M, Wong G, et al. Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors. Neurosurgery. 2011;68:1667–75.

    Article  PubMed  Google Scholar 

  61. Chen L, Wan JQ, Zhou JP, Fan YL, Jiang JY. Gene expression analysis of ruptured and un-ruptured saccular intracranial aneurysm. Eur Rev Med Pharmacol Sci. 2013;17:1374–81.

    CAS  PubMed  Google Scholar 

  62. Isaksen JG, Bazilevs Y, Kvamsdal T, Zhang Y, Kaspersen JH, Waterloo K, et al. Determination of wall tension in cerebral artery aneurysms by numerical simulation. Stroke. 2008;39:3172–8.

    Article  PubMed  Google Scholar 

  63. Cebral JR, Mut F, Weir J, Putman C. Quantitative characterization of the hemodynamic environment in ruptured and unruptured brain aneurysms. AJNR Am J Neuroradiol. 2011;32:145–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Etminan N, Dreier R, Buchholz BA, Bruckner P, Steiger HJ, Hänggi D, et al. Exploring the age of intracranial aneurysms using carbon birth dating: preliminary results. Stroke. 2013;44:799–802.

    Article  PubMed Central  PubMed  Google Scholar 

  65. Koffijberg H, Buskens E, Algra A, Wermer MJ, Rinkel GJ. Growth rates of intracranial aneurysms: exploring constancy. J Neurosurg. 2008;109:176–85.

    Article  PubMed  Google Scholar 

  66. Villablanca JP, Duckwiler GR, Jahan R, Tateshima S, Martin NA, Frazee J, et al. Natural history of asymptomatic unruptured cerebral aneurysms evaluated at CT angiography: growth and rupture incidence and correlation with epidemiologic risk factors. Radiology. 2013;269:258–65.

    Article  PubMed  Google Scholar 

  67. Hasan D, Chalouhi N, Jabbour P, Dumont AS, Kung DK, Magnotta VA, et al. Early change in ferumoxytol-enhanced magnetic resonance imaging signal suggests unstable human cerebral aneurysm: a pilot study. Stroke. 2012;43:3258–65.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Bruno G, Todor R, Lewis I, Chyatte D. Vascular extracellular matrix remodeling in cerebral aneurysms. J Neurosurg. 1998;89:431–40.

    Article  CAS  PubMed  Google Scholar 

  69. Bavinzski G, Talazoglu V, Killer M, Richling B, Gruber A, Gross CE, et al. Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils. J Neurosurg. 1999;91:284–93.

    Article  CAS  PubMed  Google Scholar 

  70. Szikora I, Seifert P, Hanzely Z, Kulcsar Z, Berentei Z, Marosfoi M, et al. Histopathologic evaluation of aneurysms treated with Guglielmi detachable coils or matrix detachable microcoils. AJNR Am J Neuroradiol. 2006;27:283–8.

    CAS  PubMed  Google Scholar 

  71. Ferns SP, Sprengers ME, van Rooij WJ, van Zwam WH, de Kort GA, Velthuis BK, et al. Late reopening of adequately coiled intracranial aneurysms: frequency and risk factors in 400 patients with 440 aneurysms. Stroke. 2011;42:1331–7.

    Article  PubMed  Google Scholar 

  72. Hayakawa M, Murayama Y, Duckwiler GR, Gobin YP, Guglielmi G, Viñuela F. Natural history of the neck remnant of a cerebral aneurysm treated with the Guglielmi detachable coil system. J Neurosurg. 2000;93:561–8.

    Article  CAS  PubMed  Google Scholar 

  73. Hasan DM, Mahaney KB, Brown RD Jr, Meissner I, Piepgras DG, Huston J, Capuano AW, Torner JC. International study of unruptured intracranial aneurysms investigators. Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke. 2011;42:3156–62.

    Google Scholar 

  74. Yoshimura Y, Murakami Y, Saitoh M, Yokoi T, Aoki T, Miura K, et al. Statin use and risk of cerebral aneurysm rupture: a hospital-based case-control study in Japan. J Stroke Cerebrovasc Dis. 2014;23:343–8.

    Article  PubMed  Google Scholar 

  75. Allaire E, Muscatelli-Groux B, Guinault AM, Pages C, Goussard A, Mandet C, et al. Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis. Ann Surg. 2004;239:417–27.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Raymond J, Desfaits AC, Roy D. Fibrinogen and vascular smooth muscle cell grafts promote healing of experimental aneurysms treated by embolization. Stroke. 1999;30:1657–64.

    Article  CAS  PubMed  Google Scholar 

  77. Ribourtout E, Desfaits AC, Salazkin I, Raymond J. Ex vivo gene therapy with adenovirus-mediated transforming growth factor beta1 expression for endovascular treatment of aneurysm: results in a canine bilateral aneurysm model. J Vasc Surg. 2003;38:576–83.

    Article  PubMed  Google Scholar 

  78. Kumar AH, Caplice NM. Clinical potential of adult vascular progenitor cells. Arterioscler Thromb Vasc Biol. 2010;30:1080–7. Review.

    Article  CAS  PubMed  Google Scholar 

  79. Schneider F, Saucy F, de Blic R, Dai J, Mohand F, Rouard H, et al. Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model. Eur J Vasc Endovasc Surg. 2013;45:666–72.

    Article  CAS  PubMed  Google Scholar 

  80. Rouchaud A, Journé C, Louedec L, Ollivier V, Derkaoui M, Michel JB, et al. Autologous mesenchymal stem cell endografting in experimental cerebrovascular aneurysms. Neuroradiology. 2013;55:741–9.

    Article  PubMed  Google Scholar 

  81. Shimizu K, Sugiyama S, Aikawa M, Fukumoto Y, Rabkin E, Libby P, et al. Host bone-marrow cells are a source of donor intimal smooth- muscle-like cells in murine aortic transplant arteriopathy. Nat Med. 2001;7:738–41.

    Article  CAS  PubMed  Google Scholar 

  82. Religa P, Bojakowski K, Maksymowicz M, Bojakowska M, Sirsjö A, Gaciong Z, et al. Smooth-muscle progenitor cells of bone marrow origin contribute to the development of neointimal thickenings in rat aortic allografts and injured rat carotid arteries. Transplantation. 2002;74:1310–5.

    Article  PubMed  Google Scholar 

  83. Caplice NM, Bunch TJ, Stalboerger PG, Wang S, Simper D, Miller DV, et al. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc Natl Acad Sci U S A. 2003;100:4754–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Iwata H, Manabe I, Fujiu K, Yamamoto T, Takeda N, Eguchi K, et al. Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages. Circulation. 2010;122:2048–57.

    Article  CAS  PubMed  Google Scholar 

  85. Daniel JM, Sedding DG. Circulating smooth muscle progenitor cells in arterial remodeling. J Mol Cell Cardiol. 2011;50:273–9.

    Article  CAS  PubMed  Google Scholar 

  86. Hoh BL, Velat GJ, Wilmer EN, Hosaka K, Fisher RC, Scott EW. A novel murine elastase saccular aneurysm model for studying bone marrow progenitor-derived cell-mediated processes in aneurysm formation. Neurosurgery. 2010;66:544–50.

    Article  PubMed Central  PubMed  Google Scholar 

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Compliance with Ethics Requirements

Dr. Juhana Frösen has received research grants from the Finnish Government, as well as from several private foundations that support medical research in Finland. In addition, Dr. Juhana Frösen has received research grants or research support from the following companies: Cook Medical, Aplagon, and Boston Scientific. Dr. Juhana Frösen has received speaker honorariums from the European Society for Minimally Invasive Neurological Therapy (ESMINT).

This article does not contain original data from research on human or animal subjects, with the exception of microphotographs from human aneurysm wall samples and from samples derived from animal models. These studies were conducted in accordance with the ethical standards of the responsible institutional committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed. The author trusts that the studies referred to in this review article have followed ethical guidelines as stated in the original publications.

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Frösen, J. Smooth Muscle Cells and the Formation, Degeneration, and Rupture of Saccular Intracranial Aneurysm Wall—a Review of Current Pathophysiological Knowledge. Transl. Stroke Res. 5, 347–356 (2014). https://doi.org/10.1007/s12975-014-0340-3

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