Skip to main content

Advertisement

SpringerLink
Log in

Vascular Smooth Muscle Cells in Cerebral Aneurysm Pathogenesis

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Vascular smooth muscle cells (SMC) maintain significant plasticity. Following environmental stimulation, SMC can alter their phenotype from one primarily concerned with contraction to a pro-inflammatory and matrix remodeling phenotype. This is a critical process behind peripheral vascular disease and atherosclerosis, a key element of cerebral aneurysm pathology. Evolving evidence demonstrates that SMCs and phenotypic modulation play a significant role in cerebral aneurysm formation and rupture. Pharmacological alteration of smooth muscle cell function and phenotypic modulation could provide a promising medical therapy to inhibit cerebral aneurysm progression. This study reviews vascular SMC function and its contribution to cerebral aneurysm pathophysiology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ICAM-1:

Intercellular adhesion molecule-1

IL-1β:

Interleukin 1β

MMP:

Matrix metalloproteinases

NF-kB:

Nuclear factor kB

NOS:

Nitric oxide synthase

PDGF:

Platelet-derived growth factor

SM-MHC:

Smooth muscle myosin heavy chain

SM-α-actin:

Smooth muscle alpha actin

SM22α:

Smooth muscle 22 alpha

SMC:

Smooth muscle cells

SSAO:

Semicarbazide-sensitive amine oxidase

TNF-α:

Tumor necrosis factor alpha

TGFβ:

Transforming growth factor β

VCAM:

Vascular cell adhesion molecule-1

References

  1. Owens GK. Molecular control of vascular smooth muscle cell differentiation and phenotypic plasticity. Novartis Found Symp. 2007;283:174–91. discussion 91–3, 238–41.

    Article  CAS  PubMed  Google Scholar 

  2. Alexander MR, Owens GK. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol. 2012;74:13–40. doi:10.1146/annurev-physiol-012110-142315.

    Article  CAS  PubMed  Google Scholar 

  3. Ali MS, Starke RM, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, et al. TNF-alpha induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology. J Cereb Blood Flow Metab. 2013. doi:10.1038/jcbfm.2013.109.

    PubMed  Google Scholar 

  4. Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res. 2012;95(2):156–64. doi:10.1093/cvr/cvs115.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 2004;84(3):767–801. doi:10.1152/physrev.00041.2003.

    Article  CAS  PubMed  Google Scholar 

  6. Rinkel GJ. Natural history, epidemiology and screening of unruptured intracranial aneurysms. J Neuroradiol. 2008;35(2):99–103.

    Article  CAS  PubMed  Google Scholar 

  7. Komotar RJ, Zacharia BE, Mocco J, Connolly Jr ES. Controversies in the surgical treatment of ruptured intracranial aneurysms: the First Annual J. Lawrence Pool Memorial Research Symposium—controversies in the management of cerebral aneurysms. Neurosurgery. 2008;62(2):396–407.

    Article  PubMed  Google Scholar 

  8. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet. 2007;369(9558):306–18.

    Article  PubMed  Google Scholar 

  9. Kassell NF, Torner JC. The International Cooperative Study on Timing of Aneurysm Surgery—an update. Stroke. 1984;15(3):566–70.

    Article  CAS  PubMed  Google Scholar 

  10. Schievink WI. Intracranial aneurysms. N Engl J Med. 1997;336(1):28–40.

    Article  CAS  PubMed  Google Scholar 

  11. Ronkainen A, Miettinen H, Karkola K, Papinaho S, Vanninen R, Puranen M, et al. Risk of harboring an unruptured intracranial aneurysm. Stroke. 1998;29(2):359–62.

    Article  CAS  PubMed  Google Scholar 

  12. Laidlaw JD, Siu KH. Ultra-early surgery for aneurysmal subarachnoid hemorrhage: outcomes for a consecutive series of 391 patients not selected by grade or age. J Neurosurg. 2002;97(2):250–8. doi:10.3171/jns.2002.97.2.0250. discussion 47–9.

    Article  PubMed  Google Scholar 

  13. Hop JW, Rinkel GJ, Algra A, van Gijn J. Quality of life in patients and partners after aneurysmal subarachnoid hemorrhage. Stroke. 1998;29(4):798–804.

    Article  CAS  PubMed  Google Scholar 

  14. Ropper AH, Zervas NT. Outcome 1 year after SAH from cerebral aneurysm. Management morbidity, mortality, and functional status in 112 consecutive good-risk patients. J Neurosurg. 1984;60(5):909–15.

    Article  CAS  PubMed  Google Scholar 

  15. 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(7):635–42. doi:10.1016/S1474-4422(09)70126-7.

    Article  PubMed  Google Scholar 

  16. Rosenorn J, Eskesen V, Schmidt K, Espersen JO, Haase J, Harmsen A, et al. Clinical features and outcome in 1076 patients with ruptured intracranial saccular aneurysms: a prospective consecutive study. Br J Neurosurg. 1987;1(1):33–45.

    Article  CAS  PubMed  Google Scholar 

  17. Saveland H, Sonesson B, Ljunggren B, Brandt L, Uski T, Zygmunt S, et al. Outcome evaluation following subarachnoid hemorrhage. J Neurosurg. 1986;64(2):191–6.

    Article  CAS  PubMed  Google Scholar 

  18. 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(9488):809–17. doi:10.1016/S0140-6736(05)67214-5.

    Article  PubMed  Google Scholar 

  19. Wiebers DO, Whisnant JP, Huston 3rd J, Meissner I, Brown Jr RD, Piepgras DG, et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362(9378):103–10.

    Article  PubMed  Google Scholar 

  20. Chalouhi N, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, et al. Biology of intracranial aneurysms: role of inflammation. J Cereb Blood Flow Metab. 2012;32(9):1659–76. doi:10.1038/jcbfm.2012.84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Hungerford JE, Little CD. Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res. 1999;36(1):2–27.

    Article  CAS  PubMed  Google Scholar 

  22. Gabbiani G, Schmid E, Winter S, Chaponnier C, de Ckhastonay C, Vandekerckhove J, et al. Vascular smooth muscle cells differ from other smooth muscle cells: predominance of vimentin filaments and a specific alpha-type actin. Proc Natl Acad Sci U S A. 1981;78(1):298–302.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Babij P, Kelly C, Periasamy M. Characterization of a mammalian smooth muscle myosin heavy-chain gene: complete nucleotide and protein coding sequence and analysis of the 5′ end of the gene. Proc Natl Acad Sci U S A. 1991;88(23):10676–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Duband JL, Gimona M, Scatena M, Sartore S, Small JV. Calponin and SM 22 as differentiation markers of smooth muscle: spatiotemporal distribution during avian embryonic development. Differentiation. 1993;55(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  25. van der Loop FT, Schaart G, Timmer ED, Ramaekers FC, van Eys GJ. Smoothelin, a novel cytoskeletal protein specific for smooth muscle cells. J Cell Biol. 1996;134(2):401–11.

    Article  PubMed  Google Scholar 

  26. Li L, Miano JM, Cserjesi P, Olson EN. SM22 alpha, a marker of adult smooth muscle, is expressed in multiple myogenic lineages during embryogenesis. Circ Res. 1996;78(2):188–95.

    Article  CAS  PubMed  Google Scholar 

  27. 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(8):4754–9. doi:10.1073/pnas.0730743100.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Stewart HJ, Guildford AL, Lawrence-Watt DJ, Santin M. Substrate-induced phenotypical change of monocytes/macrophages into myofibroblast-like cells: a new insight into the mechanism of in-stent restenosis. J Biomed Mater Res A. 2009;90(2):465–71. doi:10.1002/jbm.a.32100.

    Article  CAS  PubMed  Google Scholar 

  29. Martin K, Weiss S, Metharom P, Schmeckpeper J, Hynes B, O’Sullivan J, et al. Thrombin stimulates smooth muscle cell differentiation from peripheral blood mononuclear cells via protease-activated receptor-1, RhoA, and myocardin. Circ Res. 2009;105(3):214–8. doi:10.1161/CIRCRESAHA.109.199984.

    Article  CAS  PubMed  Google Scholar 

  30. Andreeva ER, Pugach IM, Orekhov AN. Subendothelial smooth muscle cells of human aorta express macrophage antigen in situ and in vitro. Atherosclerosis. 1997;135(1):19–27.

    Article  CAS  PubMed  Google Scholar 

  31. Rong JX, Shapiro M, Trogan E, Fisher EA. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci U S A. 2003;100(23):13531–6. doi:10.1073/pnas.1735526100.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res. 2012. doi:10.1093/cvr/cvs115.

    Google Scholar 

  33. Lee RT, Libby P. The unstable atheroma. Arterioscler Thromb Vasc Biol. 1997;17(10):1859–67.

    Article  CAS  PubMed  Google Scholar 

  34. Falk E. Why do plaques rupture? Circulation. 1992;86(6 Suppl):III30–42.

    CAS  PubMed  Google Scholar 

  35. Owens GK. Molecular control of vascular smooth muscle cell differentiation. Acta Physiol Scand. 1998;164(4):623–35.

    CAS  PubMed  Google Scholar 

  36. McDonald OG, Wamhoff BR, Hoofnagle MH, Owens GK. Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo. J Clin Invest. 2006;116(1):36–48. doi:10.1172/JCI26505.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Sano H, Sudo T, Yokode M, Murayama T, Kataoka H, Takakura N, et al. Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient mice. Circulation. 2001;103(24):2955–60.

    Article  CAS  PubMed  Google Scholar 

  38. Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW. Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest. 1992;89(2):507–11. doi:10.1172/JCI115613.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Amento EP, Ehsani N, Palmer H, Libby P. Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arterioscler Thromb. 1991;11(5):1223–30.

    Article  CAS  PubMed  Google Scholar 

  40. Johnstone SR, Ross J, Rizzo MJ, Straub AC, Lampe PD, Leitinger N, et al. Oxidized phospholipid species promote in vivo differential cx43 phosphorylation and vascular smooth muscle cell proliferation. Am J Pathol. 2009;175(2):916–24. doi:10.2353/ajpath.2009.090160.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Couffinhal T, Duplaa C, Moreau C, Lamaziere JM, Bonnet J. Regulation of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in human vascular smooth muscle cells. Circ Res. 1994;74(2):225–34.

    Article  CAS  PubMed  Google Scholar 

  42. Loppnow H, Libby P. Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. J Clin Invest. 1990;85(3):731–8. doi:10.1172/JCI114498.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Fabunmi RP, Baker AH, Murray EJ, Booth RF, Newby AC. Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1, −2, and −3 in rabbit aortic smooth muscle cells. Biochem J. 1996;315(Pt 1):335–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Speer MY, Yang HY, Brabb T, Leaf E, Look A, Lin WL, et al. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res. 2009;104(6):733–41. doi:10.1161/CIRCRESAHA.108.183053.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, et al. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol. 2008;10(3):353–60. doi:10.1038/ncb1698.

    Article  PubMed  Google Scholar 

  46. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 2007;448(7151):318–24. doi:10.1038/nature05944.

    Article  CAS  PubMed  Google Scholar 

  47. Yoshida T, Kaestner KH, Owens GK. Conditional deletion of Kruppel-like factor 4 delays downregulation of smooth muscle cell differentiation markers but accelerates neointimal formation following vascular injury. Circ Res. 2008;102(12):1548–57. doi:10.1161/CIRCRESAHA.108.176974.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Wamhoff BR, Hoofnagle MH, Burns A, Sinha S, McDonald OG, Owens GK. A G/C element mediates repression of the SM22alpha promoter within phenotypically modulated smooth muscle cells in experimental atherosclerosis. Circ Res. 2004;95(10):981–8. doi:10.1161/01.RES.0000147961.09840.fb.

    Article  CAS  PubMed  Google Scholar 

  49. Salmon M, Gomez D, Greene E, Shankman L, Owens GK. Cooperative binding of KLF4, pELK-1, and HDAC2 to a G/C repressor element in the SM22alpha promoter mediates transcriptional silencing during SMC phenotypic switching in vivo. Circ Res. 2012;111(6):685–96. doi:10.1161/CIRCRESAHA.112.269811.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Starke RM, Chalouhi N, Ali MS, Jabbour PM, Tjoumakaris SI, Gonzalez LF, et al. The role of oxidative stress in cerebral aneurysm formation and rupture. Curr Neurovasc Res. 2013;10(3):247–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Alfano JM, Kolega J, Natarajan SK, Xiang J, Paluch RA, Levy EI, et al. Intracranial aneurysms occur more frequently at bifurcation sites that typically experience higher hemodynamic stresses. Neurosurgery. 2013. doi:10.1227/NEU.0000000000000016.

    PubMed  Google Scholar 

  52. Kolega J, Gao L, Mandelbaum M, Mocco J, Siddiqui AH, Natarajan SK, et al. Cellular and molecular responses of the basilar terminus to hemodynamics during intracranial aneurysm initiation in a rabbit model. J Vasc Res. 2011;48(5):429–42. doi:10.1159/000324840.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. 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(9):1117–23. doi:10.1038/gt.2010.60.

    Article  CAS  PubMed  Google Scholar 

  54. Bygglin H, Laaksamo E, Myllarniemi M, Tulamo R, Hernesniemi J, Niemela M, et al. Isolation, culture, and characterization of smooth muscle cells from human intracranial aneurysms. Acta Neurochir (Wien). 2011;153(2):311–8. doi:10.1007/s00701-010-0836-x.

    Article  PubMed  Google Scholar 

  55. Chalouhi N, Ali MS, Starke RM, Jabbour PM, Tjoumakaris SI, Gonzalez LF, et al. Cigarette smoke and inflammation: role in cerebral aneurysm formation and rupture. Mediators Inflamm. 2012;2012:271582. doi:10.1155/2012/271582.

    PubMed Central  PubMed  Google Scholar 

  56. Kosierkiewicz TA, Factor SM, Dickson DW. Immunocytochemical studies of atherosclerotic lesions of cerebral berry aneurysms. J Neuropathol Exp Neurol. 1994;53(4):399–406.

    Article  CAS  PubMed  Google Scholar 

  57. Frosen J, Marjamaa J, Myllarniemi M, Abo-Ramadan U, Tulamo R, Niemela 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(5):936–44. doi:10.1227/01.NEU.0000210260.55124.A4. discussion −44.

    Article  PubMed  Google Scholar 

  58. Starke RM, Ali M, Jabbour P, Tjoumakaris SI, Gonzalez LF, Hasan D, et al. Cigarette smoke modulates vascular smooth muscle phenotype: implications for carotid and cerebrovascular disease. Plos One. 2013;8(8):e71954. doi:10.1371/journal.pone.0071954.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Nakajima N, Nagahiro S, Sano T, Satomi J, Satoh K. Phenotypic modulation of smooth muscle cells in human cerebral aneurysmal walls. Acta Neuropathol. 2000;100(5):475–80.

    Article  CAS  PubMed  Google Scholar 

  60. Kilic T, Sohrabifar M, Kurtkaya O, Yildirim O, Elmaci I, Gunel M, et al. Expression of structural proteins and angiogenic factors in normal arterial and unruptured and ruptured aneurysm walls. Neurosurgery. 2005;57(5):997–1007. discussion 997.

    Article  PubMed  Google Scholar 

  61. Pera J, Korostynski M, Krzyszkowski T, Czopek J, Slowik A, Dziedzic T, et al. Gene expression profiles in human ruptured and unruptured intracranial aneurysms: what is the role of inflammation? Stroke. 2010;41(2):224–31. doi:10.1161/STROKEAHA.109.562009.

    Article  CAS  PubMed  Google Scholar 

  62. Sibon I, Mercier N, Darret D, Lacolley P, Lamaziere JM. Association between semicarbazide-sensitive amine oxidase, a regulator of the glucose transporter, and elastic lamellae thinning during experimental cerebral aneurysm development: laboratory investigation. J Neurosurg. 2008;108(3):558–66. doi:10.3171/jns/2008/108/3/0558.

    Article  CAS  PubMed  Google Scholar 

  63. Merei FT, Gallyas F. Role of the structural elements of the arterial wall in the formation and growth of intracranial saccular aneurysms. Neurol Res. 1980;2(3–4):283–303.

    CAS  PubMed  Google Scholar 

  64. Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, et al. Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nat Genet. 2006;38(4):452–7. doi:10.1038/ng1764.

    Article  CAS  PubMed  Google Scholar 

  65. Ali MS, Starke RM, Jabbour P, Tjoumakaris SI, Gonzalez LF, Rosenwasser RH, et al. 184 Infliximab suppresses TNF-alpha induced inflammatory phenotype in cerebral vascular smooth muscle cells: implications for cerebral aneurysm formation. Neurosurgery. 2013;60 Suppl 1:181. doi:10.1227/01.neu.0000432774.35977.11.

    Article  Google Scholar 

  66. Chalouhi N, Points L, Pierce GL, Ballas Z, Jabbour P, Hasan D. Localized increase of chemokines in the lumen of human cerebral aneurysms. Stroke. 2013. doi:10.1161/STROKEAHA.113.002361.

    Google Scholar 

  67. 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(3):942–51. doi:10.1161/STROKEAHA.108.532556.

    Article  CAS  PubMed  Google Scholar 

  68. 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(7):1080–6. doi:10.1161/ATVBAHA.108.180760.

    Article  CAS  PubMed  Google Scholar 

  69. Aoki T, Kataoka H, Shimamura M, Nakagami H, Wakayama K, Moriwaki T, et al. NF-kappaB is a key mediator of cerebral aneurysm formation. Circulation. 2007;116(24):2830–40. doi:10.1161/CIRCULATIONAHA.107.728303.

    Article  CAS  PubMed  Google Scholar 

  70. Kim SC, Singh M, Huang J, Prestigiacomo CJ, Winfree CJ, Solomon RA, et al. Matrix metalloproteinase-9 in cerebral aneurysms. Neurosurgery. 1997;41(3):642–66. discussion 6–7.

    CAS  PubMed  Google Scholar 

  71. 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(1):162–9. doi:10.1161/01.STR.0000252129.18605.c8.

    Article  CAS  PubMed  Google Scholar 

  72. 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(3):900–5. doi:10.1161/01.STR.0000204028.39783.d9.

    Article  CAS  PubMed  Google Scholar 

  73. Fukuda S, Hashimoto N, Naritomi H, Nagata I, Nozaki K, Kondo S, et al. Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase. Circulation. 2000;101(21):2532–8.

    Article  CAS  PubMed  Google Scholar 

  74. Jayaraman T, Berenstein V, Li X, Mayer J, Silane M, Shin YS, et al. Tumor necrosis factor alpha is a key modulator of inflammation in cerebral aneurysms. Neurosurgery. 2005;57(3):558–64. discussion −64.

    Article  PubMed  Google Scholar 

  75. 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(5):469–74.

    Article  CAS  Google Scholar 

  76. Hara A, Yoshimi N, Mori H. Evidence for apoptosis in human intracranial aneurysms. Neurol Res. 1998;20(2):127–30.

    CAS  PubMed  Google Scholar 

  77. 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(6):550–5. doi:10.1016/j.jocn.2005.11.018.

    Article  CAS  PubMed  Google Scholar 

  78. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861–72. doi:10.1016/j.cell.2007.11.019.

    Article  CAS  PubMed  Google Scholar 

  79. Frosen J, Tulamo R, Paetau A, Laaksamo E, Korja M, Laakso A, et al. Saccular intracranial aneurysm: pathology and mechanisms. Acta Neuropathol. 2012;123(6):773–86. doi:10.1007/s00401-011-0939-3.

    Article  PubMed  Google Scholar 

  80. 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(7):626–36. doi:10.1016/S1474-4422(11)70109-0.

    Article  PubMed  Google Scholar 

  81. Vlak MH, Rinkel GJ, Greebe P, Algra A. Independent risk factors for intracranial aneurysms and their joint effect: a case–control study. Stroke. 2013;44(4):984–7. doi:10.1161/STROKEAHA.111.000329.

    Article  PubMed  Google Scholar 

  82. Gerzanich V, Zhang F, West GA, Simard JM. Chronic nicotine alters NO signaling of Ca(2+) channels in cerebral arterioles. Circ Res. 2001;88(3):359–65.

    Article  CAS  PubMed  Google Scholar 

  83. Starke RM, Chalouhi N, Ali MS, Jabbour P, Tjoumakaris SI, Gonzalez LF, et al. 190 critical role of TNF-a in cerebral aneurysm formation and rupture. Neurosurgery. 2013;60 Suppl 1:183. doi:10.1227/01.neu.0000432780.74094.e2.

    Article  Google Scholar 

  84. Faustman D, Davis M. TNF receptor 2 pathway: drug target for autoimmune diseases. Nat Rev Drug Discov. 2010;9(6):482–93. doi:10.1038/nrd3030.

    Article  CAS  PubMed  Google Scholar 

  85. Bonilla-Hernan MG, Miranda-Carus ME, Martin-Mola E. New drugs beyond biologics in rheumatoid arthritis: the kinase inhibitors. Rheumatology (Oxford). 2013;50(9):1542–50. doi:10.1093/rheumatology/ker192.

    Article  Google Scholar 

  86. 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(12):3258–65. doi:10.1161/STROKEAHA.112.673400.

    Article  PubMed Central  PubMed  Google Scholar 

  87. Hasan DM, Chalouhi N, Jabbour P, Dumont AS, Kung DK, Magnotta VA, et al. Evidence that acetylsalicylic acid attenuates inflammation in the walls of human cerebral aneurysms: preliminary results. J Am Heart Assoc. 2013;2(1):e000019. doi:10.1161/JAHA.112.000019.

    Article  PubMed Central  PubMed  Google Scholar 

  88. Hasan DM, Chalouhi N, Jabbour P, Magnotta VA, Kung DK, Young WL. Imaging aspirin effect on macrophages in the wall of human cerebral aneurysms using ferumoxytol-enhanced MRI: preliminary results. J Neuroradiol. 2013;40(3):187–91. doi:10.1016/j.neurad.2012.09.002.

    Article  PubMed  Google Scholar 

  89. Hasan DM, Mahaney KB, Magnotta VA, Kung DK, Lawton MT, Hashimoto T, et al. Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study. Arterioscler Thromb Vasc Biol. 2012;32(4):1032–8. doi:10.1161/ATVBAHA.111.239871.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Joseph and Marie Field Cerebrovascular Research Laboratory Endowment and by the National Institute of Neurological Disorders and Stroke [1K08NS067072 to ASD].

Conflict of Interest

None declared.

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA

    Robert M. Starke, Dale Ding, Daniel M. S. Raper & M. Sean Mckisic

  2. Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA

    Nohra Chalouhi

  3. Department of Molecular Physiology and Biophysics, Robert M. Berne Cardiovascular Research Center, Charlottesville, VA, USA

    Gary K. Owens

  4. Department of Neurological Surgery, University of Iowa, Iowa City, IA, USA

    David M. Hasan

  5. Department of Neurological Surgery, Tulane University, 131 S. Robertson St., Suite 1300, New Orleans, LA, 70112, USA

    Ricky Medel & Aaron S. Dumont

Authors
  1. Robert M. Starke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nohra Chalouhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dale Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel M. S. Raper
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Sean Mckisic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gary K. Owens
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David M. Hasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ricky Medel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aaron S. Dumont
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aaron S. Dumont.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Starke, R.M., Chalouhi, N., Ding, D. et al. Vascular Smooth Muscle Cells in Cerebral Aneurysm Pathogenesis. Transl. Stroke Res. 5, 338–346 (2014). https://doi.org/10.1007/s12975-013-0290-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-013-0290-1

Keywords

Search

Navigation