nach oben

NeuroMolecular Medicine

Erschienen in:

04.05.2019 | Review Paper

Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms

verfasst von: Zhen Xu, Yan-Ning Rui, John P. Hagan, Dong H. Kim

Erschienen in: NeuroMolecular Medicine | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

Intracranial aneurysms (IA) are local dilatations in cerebral arteries that predominantly affect the circle of Willis. Occurring in approximately 2–5% of adults, these weakened areas are susceptible to rupture, leading to subarachnoid hemorrhage (SAH), a type of hemorrhagic stroke. Due to its early age of onset and poor prognosis, SAH accounts for > 25% of years lost for all stroke victims under the age of 65. In this review, we describe the cerebrovascular pathology associated with intracranial aneurysms. To understand IA genetics, we summarize syndromes with elevated incidence, genome-wide association studies (GWAS), whole exome studies on IA-affected families, and recent research that established definitive roles for Thsd1 (Thrombospondin Type 1 Domain Containing Protein 1) and Sox17 (SRY-box 17) in IA using genetically engineered mouse models. Lastly, we discuss the underlying molecular mechanisms of IA, including defects in vascular endothelial and smooth muscle cells caused by dysfunction in mechanotransduction, Thsd1/FAK (Focal Adhesion Kinase) signaling, and the Transforming Growth Factor β (TGF-β) pathway. As illustrated by THSD1 research, cell adhesion may play a significant role in IA.

AbouAlaiwi, W. A., Takahashi, M., Mell, B. R., Jones, T. J., Ratnam, S., Kolb, R. J., et al. (2009). Ciliary polycystin-2 is a mechanosensitive calcium channel involved in nitric oxide signaling cascades. Circulation Research,104(7), 860–869. https://doi.org/10.1161/CIRCRESAHA.108.192765.CrossRefPubMedPubMedCentral

Abrantes, P., Santos, M. M., Sousa, I., Xavier, J. M., Francisco, V., Krug, T., et al. (2015). Genetic variants underlying risk of intracranial aneurysms: Insights from a GWAS in Portugal. PLoS ONE,10(7), e0133422. https://doi.org/10.1371/journal.pone.0133422.CrossRefPubMedPubMedCentral

Akagawa, H., Tajima, A., Sakamoto, Y., Krischek, B., Yoneyama, T., Kasuya, H., et al. (2006). A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and confers susceptibility to intracranial aneurysms. Human Molecular Genetics,15(10), 1722–1734. https://doi.org/10.1093/hmg/ddl096.CrossRefPubMed

Akiyama, K., Narita, A., Nakaoka, H., Cui, T., Takahashi, T., Yasuno, K., et al. (2010). Genome-wide association study to identify genetic variants present in Japanese patients harboring intracranial aneurysms. Journal of Human Genetics,55(10), 656–661. https://doi.org/10.1038/jhg.2010.82.CrossRefPubMed

Alg, V. S., Ke, X., Grieve, J., Bonner, S., Walsh, D. C., Bulters, D., et al. (2018). Association of functional MMP-2 gene variant with intracranial aneurysms: Case-control genetic association study and meta-analysis. British Journal of Neurosurgery,32(3), 255–259. https://doi.org/10.1080/02688697.2018.1427213.CrossRefPubMed

Alg, V. S., Sofat, R., Houlden, H., & Werring, D. J. (2013). Genetic risk factors for intracranial aneurysms: A meta-analysis in more than 116,000 individuals. Neurology,80(23), 2154–2165. https://doi.org/10.1212/WNL.0b013e318295d751.CrossRefPubMedPubMedCentral

Andreasen, T. H., Bartek, J., Jr., Andresen, M., Springborg, J. B., & Romner, B. (2013). Modifiable risk factors for aneurysmal subarachnoid hemorrhage. Stroke,44(12), 3607–3612. https://doi.org/10.1161/STROKEAHA.113.001575.CrossRefPubMed

Aoki, T., Kataoka, H., Ishibashi, R., Nozaki, K., Egashira, K., & Hashimoto, N. (2009). Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation. Stroke,40(3), 942–951. https://doi.org/10.1161/STROKEAHA.108.532556.CrossRefPubMed

Aoki, T., Kataoka, H., Shimamura, M., Nakagami, H., Wakayama, K., Moriwaki, T., et al. (2007). NF-kappaB is a key mediator of cerebral aneurysm formation. Circulation,116(24), 2830–2840. https://doi.org/10.1161/CIRCULATIONAHA.107.728303.CrossRefPubMed

Aoki, T., & Nishimura, M. (2011). The development and the use of experimental animal models to study the underlying mechanisms of CA formation. Journal of Biomedicine and Biotechnology,2011, 535921. https://doi.org/10.1155/2011/535921.CrossRefPubMed

Aoki, T., Saito, M., Koseki, H., Tsuji, K., Tsuji, A., Murata, K., et al. (2017). Macrophage imaging of cerebral aneurysms with ferumoxytol: An exploratory study in an animal model and in patients. The Journal of Stroke & Cerebrovascular Diseases,26(10), 2055–2064. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.10.026.CrossRef

Arning, A., Jeibmann, A., Kohnemann, S., Brokinkel, B., Ewelt, C., Berger, K., et al. (2016). ADAMTS genes and the risk of cerebral aneurysm. Journal of Neurosurgery,125(2), 269–274. https://doi.org/10.3171/2015.7.JNS154.CrossRefPubMed

Batra, R., Suh, M. K., Carson, J. S., Dale, M. A., Meisinger, T. M., Fitzgerald, M., et al. (2018). IL-1beta (interleukin-1beta) and TNF-alpha (tumor necrosis factor-alpha) impact abdominal aortic aneurysm formation by differential effects on macrophage polarization. Arteriosclerosis, Thrombosis, and Vascular Biology,38(2), 457–463. https://doi.org/10.1161/ATVBAHA.117.310333.CrossRefPubMed

Bergmann, C., Guay-Woodford, L. M., Harris, P. C., Horie, S., Peters, D. J. M., & Torres, V. E. (2018). Polycystic kidney disease. Nature Reviews Disease Primers,4(1), 50. https://doi.org/10.1038/s41572-018-0047-y.CrossRefPubMedPubMedCentral

Bilguvar, K., Yasuno, K., Niemela, M., Ruigrok, Y. M., von Und, Zu, Fraunberg, M., et al. (2008). Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nature Genetics,40(12), 1472–1477. https://doi.org/10.1038/ng.240.CrossRefPubMedPubMedCentral

Bober, M. B., Khan, N., Kaplan, J., Lewis, K., Feinstein, J. A., Scott, C. I., Jr., et al. (2010). Majewski osteodysplastic primordial dwarfism type II (MOPD II): Expanding the vascular phenotype. The American Journal of Medical Genetics - Part A,152A(4), 960–965. https://doi.org/10.1002/ajmg.a.33252.CrossRefPubMed

Bor, A. S., Rinkel, G. J., Adami, J., Koffijberg, H., Ekbom, A., Buskens, E., et al. (2008). Risk of subarachnoid haemorrhage according to number of affected relatives: A population based case-control study. Brain,131(Pt 10), 2662–2665. https://doi.org/10.1093/brain/awn187.CrossRefPubMed

Bourcier, R., Le Scouarnec, S., Bonnaud, S., Karakachoff, M., Bourcereau, E., Heurtebise-Chretien, S., et al. (2018). Rare coding variants in ANGPTL6 are associated with familial forms of intracranial aneurysm. American Journal of Human Genetics,102(1), 133–141. https://doi.org/10.1016/j.ajhg.2017.12.006.CrossRefPubMedPubMedCentral

Bouzeghrane, F., Naggara, O., Kallmes, D. F., Berenstein, A., Raymond, J., & International Consortium of Neuroendovascular, C. (2010). In vivo experimental intracranial aneurysm models: A systematic review. AJNR American Journal of Neuroradiology,31(3), 418–423. https://doi.org/10.3174/ajnr.A1853.CrossRef

Brain Aneurysm Foundation. (2017). Brain aneurysm statistics and facts. Retrieved May 8, 2017 https://www.bafound.org/about-brain-aneurysms/brain-aneurysm-basics/brain-aneurysm-statistics-and-facts/.

Brancati, F., Castori, M., Mingarelli, R., & Dallapiccola, B. (2005). Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: Clinical report and review of cerebral vascular anomalies. The American Journal of Medical Genetics,139(3), 212–215. https://doi.org/10.1002/ajmg.a.31009.CrossRefPubMed

Bromberg, J. E., Rinkel, G. J., Algra, A., Greebe, P., van Duyn, C. M., Hasan, D., et al. (1995). Subarachnoid haemorrhage in first and second degree relatives of patients with subarachnoid haemorrhage. BMJ,311(7000), 288–289.CrossRef

Cagnazzo, F., Gambacciani, C., Morganti, R., & Perrini, P. (2017). Intracranial aneurysms in patients with autosomal dominant polycystic kidney disease: Prevalence, risk of rupture, and management. A systematic review. Acta Neurochirurgica,159(5), 811–821. https://doi.org/10.1007/s00701-017-3142-z.CrossRefPubMed

Canham, P. B., Talman, E. A., Finlay, H. M., & Dixon, J. G. (1991). Medial collagen organization in human arteries of the heart and brain by polarized light microscopy. Connective Tissue Research,26(1–2), 121–134.CrossRef

Chalouhi, N., Ali, M. S., Jabbour, P. M., Tjoumakaris, S. I., Gonzalez, L. F., Rosenwasser, R. H., et al. (2012). Biology of intracranial aneurysms: Role of inflammation. Journal of Cerebral Blood Flow and Metabolism,32(9), 1659–1676. https://doi.org/10.1038/jcbfm.2012.84.CrossRefPubMedPubMedCentral

Chu, Y., Wilson, K., Gu, H., Wegman-Points, L., Dooley, S. A., Pierce, G. L., et al. (2015). Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice. Stroke,46(6), 1651–1656. https://doi.org/10.1161/STROKEAHA.114.008589.CrossRefPubMedPubMedCentral

Conway, J. E., Hutchins, G. M., & Tamargo, R. J. (1999). Marfan syndrome is not associated with intracranial aneurysms. Stroke,30(8), 1632–1636.CrossRef

Conway, J. E., Hutchins, G. M., & Tamargo, R. J. (2001). Lack of evidence for an association between neurofibromatosis type I and intracranial aneurysms: autopsy study and review of the literature. Stroke,32(11), 2481–2485.CrossRef

Crist, A. M., Lee, A. R., Patel, N. R., Westhoff, D. E., & Meadows, S. M. (2018). Vascular deficiency of Smad4 causes arteriovenous malformations: A mouse model of Hereditary Hemorrhagic Telangiectasia. Angiogenesis,21(2), 363–380. https://doi.org/10.1007/s10456-018-9602-0.CrossRefPubMedPubMedCentral

Cun, Y. P., Xiong, C. J., Diao, B., Yang, Y., Pan, L., & Ma, L. T. (2017). Association between angiotensin-converting enzyme insertion/deletion polymorphisms and intracranial aneurysm susceptibility: A meta-analysis. Biomedical Reports,6(6), 663–670. https://doi.org/10.3892/br.2017.893.CrossRefPubMedPubMedCentral

de Hoog, C. L., Foster, L. J., & Mann, M. (2004). RNA and RNA binding proteins participate in early stages of cell spreading through spreading initiation centers. Cell,117(5), 649–662.CrossRef

De Paepe, A., & Malfait, F. (2012). The Ehlers-Danlos syndrome, a disorder with many faces. Clinical Genetics,82(1), 1–11. https://doi.org/10.1111/j.1399-0004.2012.01858.x.CrossRefPubMed

Deka, R., Koller, D. L., Lai, D., Indugula, S. R., Sun, G., Woo, D., et al. (2010). The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm. Stroke,41(6), 1132–1137. https://doi.org/10.1161/STROKEAHA.109.574640.CrossRefPubMedPubMedCentral

Deng, Q., Huo, Y., & Luo, J. (2014). Endothelial mechanosensors: The gatekeepers of vascular homeostasis and adaptation under mechanical stress. Science China Life Sciences,57(8), 755–762. https://doi.org/10.1007/s11427-014-4705-3.CrossRefPubMed

Diagbouga, M. R., Morel, S., Bijlenga, P., & Kwak, B. R. (2018). Role of hemodynamics in initiation/growth of intracranial aneurysms. European Journal of Clinical Investigation,48(9), e12992. https://doi.org/10.1111/eci.12992.CrossRefPubMed

Dietz, H. C., Saraiva, J. M., Pyeritz, R. E., Cutting, G. R., & Francomano, C. A. (1992). Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains. Human Mutation,1(5), 366–374. https://doi.org/10.1002/humu.1380010504.CrossRefPubMed

Draghia, F., Draghia, A. C., & Onicescu, D. (2008). Electron microscopic study of the arterial wall in the cerebral aneurysms. Romanian Journal of Morphology and Embryology,49(1), 101–103.PubMed

Fan, J., Sun, W., Lin, M., Yu, K., Wang, J., Duan, D., et al. (2016). Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms. Oncotarget,7(13), 16104–16111. https://doi.org/10.18632/oncotarget.7546.CrossRefPubMedPubMedCentral

Farlow, J. L., Lin, H., Sauerbeck, L., Lai, D., Koller, D. L., Pugh, E., et al. (2015). Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm. PLoS ONE,10(3), e0121104. https://doi.org/10.1371/journal.pone.0121104.CrossRefPubMedPubMedCentral

Farnham, J. M., Camp, N. J., Neuhausen, S. L., Tsuruda, J., Parker, D., MacDonald, J., et al. (2004). Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysm. Human Genetics,114(3), 250–255. https://doi.org/10.1007/s00439-003-1044-z.CrossRefPubMed

Fennell, V. S., Kalani, M. Y., Atwal, G., Martirosyan, N. L., & Spetzler, R. F. (2016). Biology of saccular cerebral aneurysms: A review of current understanding and future directions. Frontiers in Surgery,3, 43. https://doi.org/10.3389/fsurg.2016.00043.CrossRefPubMedPubMedCentral

Finlay, H. M., McCullough, L., & Canham, P. B. (1995). Three-dimensional collagen organization of human brain arteries at different transmural pressures. Journal of Vascular Research,32(5), 301–312. https://doi.org/10.1159/000159104.CrossRefPubMed

Finlay, H. M., Whittaker, P., & Canham, P. B. (1998). Collagen organization in the branching region of human brain arteries. Stroke,29(8), 1595–1601.CrossRef

Finney, L. H., Roberts, T. S., & Anderson, R. E. (1976). Giant intracranial aneurysm associated with Marfan’s syndrome. Case report. Journal of Neurosurgery,45(3), 342–347. https://doi.org/10.3171/jns.1976.45.3.0342.CrossRefPubMed

Forbus, W. D. (1930). On the origin of miliary aneurysms of the superficial cerebral arteries. Bulletin of the Johns Hopkins Hospital,47, 239–284.

Foroud, T., Koller, D. L., Lai, D., Sauerbeck, L., Anderson, C., Ko, N., et al. (2012). Genome-wide association study of intracranial aneurysms confirms role of Anril and SOX17 in disease risk. Stroke,43(11), 2846–2852. https://doi.org/10.1161/STROKEAHA.112.656397.CrossRefPubMedPubMedCentral

Foroud, T., Lai, D., Koller, D., Van’t Hof, F., Kurki, M. I., Anderson, C. S., et al. (2014). Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7. Stroke,45(11), 3194–3199. https://doi.org/10.1161/STROKEAHA.114.006096.CrossRefPubMedPubMedCentral

Foroud, T., Sauerbeck, L., Brown, R., Anderson, C., Woo, D., Kleindorfer, D., et al. (2009). Genome screen in familial intracranial aneurysm. BMC Medical Genetics,10, 3. https://doi.org/10.1186/1471-2350-10-3.CrossRefPubMedPubMedCentral

Foroud, T., Sauerbeck, L., Brown, R., Anderson, C., Woo, D., Kleindorfer, D., et al. (2008). Genome screen to detect linkage to intracranial aneurysm susceptibility genes: The Familial Intracranial Aneurysm (FIA) study. Stroke,39(5), 1434–1440. https://doi.org/10.1161/STROKEAHA.107.502930.CrossRefPubMedPubMedCentral

Gan, Q., Liu, Q., Hu, X., & You, C. (2017). Collagen type I alpha 2 (COL1A2) polymorphism contributes to intracranial aneurysm susceptibility: A meta-analysis. Medical Science Monitor,23, 3240–3246.CrossRef

Givens, C., & Tzima, E. (2016). Endothelial mechanosignaling: Does one sensor fit all? Antioxidants & Redox Signaling,25(7), 373–388. https://doi.org/10.1089/ars.2015.6493.CrossRef

Glasker, S., Schatlo, B., Klingler, J. H., Braun, V., Spangenberg, P., Kim, I. S., et al. (2014). Associations of collagen type I alpha2 polymorphisms with the presence of intracranial aneurysms in patients from Germany. The Journal of Stroke and Cerebrovascular Diseases,23(2), 356–360. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.04.038.CrossRefPubMed

Haasdijk, R. A., Den Dekker, W. K., Cheng, C., Tempel, D., Szulcek, R., Bos, F. L., et al. (2016). THSD1 preserves vascular integrity and protects against intraplaque haemorrhaging in ApoE−/− mice. Cardiovascular Research,110(1), 129–139. https://doi.org/10.1093/cvr/cvw015.CrossRefPubMed

Hainsworth, P. J., & Mendelow, A. D. (1991). Giant intracranial aneurysm associated with Marfan’s syndrome: A case report. Journal of Neurology, Neurosurgery and Psychiatry,54(5), 471–472.CrossRef

Harburger, D. S., & Calderwood, D. A. (2009). Integrin signalling at a glance. Journal of Cell Science,122(Pt 2), 159–163. https://doi.org/10.1242/jcs.018093.CrossRefPubMed

Hateboer, N., v Dijk, M. A., Bogdanova, N., Coto, E., Saggar-Malik, A. K., San Millan, J. L., et al. (1999). Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet,353(9147), 103–107.CrossRef

Hayward, C., Keston, M., Brock, D. J., & Dietz, H. C. (1992). Fibrillin (FBN1) mutations in Marfan syndrome. Human Mutation,1(1), 79. https://doi.org/10.1002/humu.1380010115.CrossRefPubMed

Higashida, R. T., Halbach, V. V., Hieshima, G. B., & Cahan, L. (1988). Cavernous carotid artery aneurysm associated with Marfan’s syndrome: Treatment by balloon embolization therapy. Neurosurgery,22(2), 297–300.CrossRef

Hitchcock, E., & Gibson, W. T. (2017). A review of the genetics of intracranial berry aneurysms and implications for genetic counseling. Journal of Genetic Counseling,26(1), 21–31. https://doi.org/10.1007/s10897-016-0029-8.CrossRefPubMed

Hong, E. P., Jeon, J. P., Kim, S. E., Yang, J. S., Choi, H. J., Kang, S. H., et al. (2017). A novel association between lysyl oxidase gene polymorphism and intracranial aneurysm in Koreans. Yonsei Medical Journal,58(5), 1006–1011. https://doi.org/10.3349/ymj.2017.58.5.1006.CrossRefPubMedPubMedCentral

Hop, J. W., Rinkel, G. J., Algra, A., & van Gijn, J. (1997). Case-fatality rates and functional outcome after subarachnoid hemorrhage: A systematic review. Stroke,28(3), 660–664.CrossRef

Hu, J., Luo, J., Wang, H., Wang, C., Sun, X., Li, A., et al. (2017). Association of TNF-alpha-3959T/C gene polymorphisms in the Chinese population with intracranial aneurysms. Journal of Molecular Neuroscience,63(3–4), 349–354. https://doi.org/10.1007/s12031-017-0985-y.CrossRefPubMed

Hu, X., Fang, Y., Li, Y. K., Liu, W. K., Li, H., Ma, L., et al. (2015). Role of endoglin insertion and rs1800956 polymorphisms in intracranial aneurysm susceptibility: A meta-analysis. Medicine (Baltimore),94(45), e1847. https://doi.org/10.1097/MD.0000000000001847.CrossRef

Iida, A., Wang, Z., Hirata, H., & Sehara-Fujisawa, A. (2018). Integrin beta1 activity is required for cardiovascular formation in zebrafish. Genes to Cells,23(11), 938–951. https://doi.org/10.1111/gtc.12641.CrossRefPubMed

International Study of Unruptured Intracranial Aneurysms (1998). Unruptured intracranial aneurysms–risk of rupture and risks of surgical intervention. New England Journal of Medicine,339(24), 1725–1733. https://doi.org/10.1056/NEJM199812103392401.CrossRef

Ishibashi, R., Aoki, T., Nishimura, M., Hashimoto, N., & Miyamoto, S. (2010). Contribution of mast cells to cerebral aneurysm formation. Current Neurovascular Research,7(2), 113–124.CrossRef

Itoh, F., Itoh, S., Adachi, T., Ichikawa, K., Matsumura, Y., Takagi, T., et al. (2012). Smad2/Smad3 in endothelium is indispensable for vascular stability via S1PR1 and N-cadherin expressions. Blood,119(22), 5320–5328. https://doi.org/10.1182/blood-2011-12-395772.CrossRefPubMedPubMedCentral

Johnston, S. C., Selvin, S., & Gress, D. R. (1998). The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology,50(5), 1413–1418.CrossRef

Joo, S. P., Kim, T. S., Lee, I. K., Lee, J. K., Seo, B. R., Kim, J. H., et al. (2009). The role of collagen type I alpha2 polymorphisms: intracranial aneurysms in Koreans. Surgical Neurology,72(1), 48–53. https://doi.org/10.1016/j.surneu.2009.02.009 (discussion 53).CrossRefPubMed

Joo, S. P., Lee, J. K., Kim, T. S., Kim, M. K., Lee, I. K., Seo, B. R., et al. (2008). A polymorphic variant of the endoglin gene is associated with increased risk for intracranial aneurysms in a Korean population. Surgical Neurology,70(1), 39–44. https://doi.org/10.1016/j.surneu.2008.01.060.CrossRefPubMed

Jurczyk, A., Gromley, A., Redick, S., San Agustin, J., Witman, G., Pazour, G. J., et al. (2004). Pericentrin forms a complex with intraflagellar transport proteins and polycystin-2 and is required for primary cilia assembly. Journal of Cell Biology,166(5), 637–643. https://doi.org/10.1083/jcb.200405023.CrossRefPubMed

Kallakuri, S., Yu, J. A., Li, J., Li, Y., Weinstein, B. M., Nicoli, S., et al. (2015). Endothelial cilia are essential for developmental vascular integrity in zebrafish. Journal of the American Society of Nephrology,26(4), 864–875. https://doi.org/10.1681/ASN.2013121314.CrossRefPubMed

Kanematsu, Y., Kanematsu, M., Kurihara, C., Tada, Y., Tsou, T. L., van Rooijen, N., et al. (2011). Critical roles of macrophages in the formation of intracranial aneurysm. Stroke,42(1), 173–178. https://doi.org/10.1161/STROKEAHA.110.590976.CrossRefPubMed

Kim, C. J., Park, S. S., Lee, H. S., Chung, H. J., Choi, W., Chung, J. H., et al. (2011). Identification of an autosomal dominant locus for intracranial aneurysm through a model-based family collection in a geographically limited area. Journal of Human Genetics,56(6), 464–466. https://doi.org/10.1038/jhg.2011.27.CrossRefPubMed

Kim, D. H., Van Ginhoven, G., & Milewicz, D. M. (2003). Incidence of familial intracranial aneurysms in 200 patients: Comparison among Caucasian, African-American, and Hispanic populations. Neurosurgery,53(2), 302–308.CrossRef

Kim, S. T., Brinjikji, W., & Kallmes, D. F. (2016). Prevalence of intracranial aneurysms in patients with connective tissue diseases: A retrospective study. AJNR American Journal of Neuroradiology,37(8), 1422–1426. https://doi.org/10.3174/ajnr.A4718.CrossRefPubMed

Kondo, S., Hashimoto, N., Kikuchi, H., Hazama, F., Nagata, I., & Kataoka, H. (1998). Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke,29(1), 181–188 (discussion 189).CrossRef

Korja, M., Silventoinen, K., Laatikainen, T., Jousilahti, P., Salomaa, V., Hernesniemi, J., et al. (2013). Risk factors and their combined effects on the incidence rate of subarachnoid hemorrhage—A population-based cohort study. PLoS ONE,8(9), e73760. https://doi.org/10.1371/journal.pone.0073760.CrossRefPubMedPubMedCentral

Korja, M., Silventoinen, K., McCarron, P., Zdravkovic, S., Skytthe, A., Haapanen, A., et al. (2010). Genetic epidemiology of spontaneous subarachnoid hemorrhage: Nordic Twin Study. Stroke,41(11), 2458–2462. https://doi.org/10.1161/STROKEAHA.110.586420.CrossRefPubMed

Krings, T., Mandell, D. M., Kiehl, T. R., Geibprasert, S., Tymianski, M., Alvarez, H., et al. (2011). Intracranial aneurysms: From vessel wall pathology to therapeutic approach. Nature Reviews Neurology,7(10), 547–559. https://doi.org/10.1038/nrneurol.2011.136.CrossRefPubMed

Krischek, B., Tajima, A., Akagawa, H., Narita, A., Ruigrok, Y., Rinkel, G., et al. (2010). Association of the Jun dimerization protein 2 gene with intracranial aneurysms in Japanese and Korean cohorts as compared to a Dutch cohort. Neuroscience,169(1), 339–343. https://doi.org/10.1016/j.neuroscience.2010.05.002.CrossRefPubMed

Kurki, M. I., Gaal, E. I., Kettunen, J., Lappalainen, T., Menelaou, A., Anttila, V., et al. (2014). High risk population isolate reveals low frequency variants predisposing to intracranial aneurysms. PLoS Genetics,10(1), e1004134. https://doi.org/10.1371/journal.pgen.1004134.CrossRefPubMedPubMedCentral

Lee, S., Kim, I. K., Ahn, J. S., Woo, D. C., Kim, S. T., Song, S., et al. (2015). Deficiency of endothelium-specific transcription factor Sox17 induces intracranial aneurysm. Circulation,131(11), 995–1005. https://doi.org/10.1161/CIRCULATIONAHA.114.012568.CrossRefPubMed

Li, F. F., Wang, X. D., Zhu, M. W., Lou, Z. H., Zhang, Q., Zhu, C. Y., et al. (2015). Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms. Metabolic Brain Disease,30(6), 1387–1394. https://doi.org/10.1007/s11011-015-9712-y.CrossRefPubMed

Linn, F. H., Rinkel, G. J., Algra, A., & van Gijn, J. (1996). Incidence of subarachnoid hemorrhage: Role of region, year, and rate of computed tomography: A meta-analysis. Stroke,27(4), 625–629.CrossRef

Liu, J., Zeng, L., Kennedy, R. M., Gruenig, N. M., & Childs, S. J. (2012). betaPix plays a dual role in cerebral vascular stability and angiogenesis, and interacts with integrin alphavbeta8. Developmental Biology,363(1), 95–105. https://doi.org/10.1016/j.ydbio.2011.12.022.CrossRefPubMed

Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., et al. (2006). Aneurysm syndromes caused by mutations in the TGF-beta receptor. New England Journal of Medicine,355(8), 788–798. https://doi.org/10.1056/NEJMoa055695.CrossRefPubMed

Lorenzo-Betancor, O., Blackburn, P. R., Edwards, E., Vazquez-do-Campo, R., Klee, E. W., Labbe, C., et al. (2018). PCNT point mutations and familial intracranial aneurysms. Neurology,91(23), e2170–e2181. https://doi.org/10.1212/WNL.0000000000006614.CrossRefPubMed

Low, S. K., Takahashi, A., Cha, P. C., Zembutsu, H., Kamatani, N., Kubo, M., et al. (2012). Genome-wide association study for intracranial aneurysm in the Japanese population identifies three candidate susceptible loci and a functional genetic variant at EDNRA. Human Molecular Genetics,21(9), 2102–2110. https://doi.org/10.1093/hmg/dds020.CrossRefPubMed

Low, S. K., Zembutsu, H., Takahashi, A., Kamatani, N., Cha, P. C., Hosono, N., et al. (2011). Impact of LIMK1, MMP2 and TNF-alpha variations for intracranial aneurysm in Japanese population. Journal of Human Genetics,56(3), 211–216. https://doi.org/10.1038/jhg.2010.169.CrossRefPubMed

MacCarrick, G., Black, J. H., 3rd, Bowdin, S., El-Hamamsy, I., Frischmeyer-Guerrerio, P. A., Guerrerio, A. L., et al. (2014). Loeys-Dietz syndrome: A primer for diagnosis and management. Genetics in Medicine,16(8), 576–587. https://doi.org/10.1038/gim.2014.11.CrossRefPubMedPubMedCentral

Mackey, J., Brown, R. D., Sauerbeck, L., Hornung, R., Moomaw, C. J., Koller, D. L., et al. (2015). Affected twins in the familial intracranial aneurysm study. Cerebrovascular Diseases,39(2), 82–86. https://doi.org/10.1159/000369961.CrossRefPubMed

Malfait, F. (2018). Vascular aspects of the Ehlers-Danlos Syndromes. Matrix Biology,71–72, 380–395. https://doi.org/10.1016/j.matbio.2018.04.013.CrossRefPubMed

Matsuda, M., Matsuda, I., Handa, H., & Okamoto, K. (1979). Intracavernous giant aneurysm associated with Marfan’s syndrome. Surgical Neurology,12(2), 119–121.PubMed

Meng, H., Tutino, V. M., Xiang, J., & Siddiqui, A. (2014). High WSS or low WSS? Complex interactions of hemodynamics with intracranial aneurysm initiation, growth, and rupture: Toward a unifying hypothesis. AJNR American Journal of Neuroradiology,35(7), 1254–1262. https://doi.org/10.3174/ajnr.A3558.CrossRefPubMed

Meng, H., Wang, Z., Hoi, Y., Gao, L., Metaxa, E., Swartz, D. D., et al. (2007). Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke,38(6), 1924–1931. https://doi.org/10.1161/STROKEAHA.106.481234.CrossRefPubMedPubMedCentral

Mineharu, Y., Inoue, K., Inoue, S., Yamada, S., Nozaki, K., Hashimoto, N., et al. (2007). Model-based linkage analyses confirm chromosome 19q13.3 as a susceptibility locus for intracranial aneurysm. Stroke,38(4), 1174–1178. https://doi.org/10.1161/01.str.0000259657.73682.03.CrossRefPubMed

Miyata, H., Koseki, H., Takizawa, K., Kasuya, H., Nozaki, K., Narumiya, S., et al. (2017). T cell function is dispensable for intracranial aneurysm formation and progression. PLoS ONE,12(4), e0175421. https://doi.org/10.1371/journal.pone.0175421.CrossRefPubMedPubMedCentral

Montero-Balaguer, M., Swirsding, K., Orsenigo, F., Cotelli, F., Mione, M., & Dejana, E. (2009). Stable vascular connections and remodeling require full expression of VE-cadherin in zebrafish embryos. PLoS ONE,4(6), e5772. https://doi.org/10.1371/journal.pone.0005772.CrossRefPubMedPubMedCentral

Morimoto, M., Miyamoto, S., Mizoguchi, A., Kume, N., Kita, T., & Hashimoto, N. (2002). Mouse model of cerebral aneurysm: Experimental induction by renal hypertension and local hemodynamic changes. Stroke,33(7), 1911–1915.CrossRef

Nader, G. P., Ezratty, E. J., & Gundersen, G. G. (2016). FAK, talin and PIPKIgamma regulate endocytosed integrin activation to polarize focal adhesion assembly. Nature Cell Biology,18(5), 491–503. https://doi.org/10.1038/ncb3333.CrossRefPubMed

Nahed, B. V., Seker, A., Guclu, B., Ozturk, A. K., Finberg, K., Hawkins, A. A., et al. (2005). Mapping a Mendelian form of intracranial aneurysm to 1p34.3-p36.13. American Journal of Human Genetics, 76(1), 172–179. https://doi.org/10.1086/426953.CrossRef

Nakajima-Takagi, Y., Osawa, M., Oshima, M., Takagi, H., Miyagi, S., Endoh, M., et al. (2013). Role of SOX17 in hematopoietic development from human embryonic stem cells. Blood,121(3), 447–458. https://doi.org/10.1182/blood-2012-05-431403.CrossRefPubMed

Nauli, S. M., Kawanabe, Y., Kaminski, J. J., Pearce, W. J., Ingber, D. E., & Zhou, J. (2008). Endothelial cilia are fluid shear sensors that regulate calcium signaling and nitric oxide production through polycystin-1. Circulation,117(9), 1161–1171. https://doi.org/10.1161/CIRCULATIONAHA.107.710111.CrossRefPubMedPubMedCentral

Nicholls, A. C., De Paepe, A., Narcisi, P., Dalgleish, R., De Keyser, F., Matton, M., et al. (1988). Linkage of a polymorphic marker for the type III collagen gene (COL3A1) to atypical autosomal dominant Ehlers-Danlos syndrome type IV in a large Belgian pedigree. Human Genetics,78(3), 276–281.CrossRef

Norrgard, O., Angquist, K. A., Fodstad, H., Forsell, A., & Lindberg, M. (1987). Intracranial aneurysms and heredity. Neurosurgery,20(2), 236–239.CrossRef

Nuki, Y., Tsou, T. L., Kurihara, C., Kanematsu, M., Kanematsu, Y., & Hashimoto, T. (2009). Elastase-induced intracranial aneurysms in hypertensive mice. Hypertension,54(6), 1337–1344. https://doi.org/10.1161/HYPERTENSIONAHA.109.138297.CrossRefPubMedPubMedCentral

Ohtsuki, H., Sugiura, M., Iwaki, K., Nishikawa, M., & Yasuno, M. (1984). A case of Marfan’s syndrome with a ruptured distal middle cerebral aneurysm. No Shinkei Geka,12(8), 983–985.PubMed

Olson, J. M., Vongpunsawad, S., Kuivaniemi, H., Ronkainen, A., Hernesniemi, J., Ryynanen, M., et al. (2002). Search for intracranial aneurysm susceptibility gene(s) using Finnish families. BMC Medical Genetics,3, 7.CrossRef

Onda, H., Kasuya, H., Yoneyama, T., Takakura, K., Hori, T., Takeda, J., et al. (2001). Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. American Journal of Human Genetics,69(4), 804–819. https://doi.org/10.1086/323614.CrossRefPubMedPubMedCentral

Ozturk, A. K., Nahed, B. V., Bydon, M., Bilguvar, K., Goksu, E., Bademci, G., et al. (2006). Molecular genetic analysis of two large kindreds with intracranial aneurysms demonstrates linkage to 11q24-25 and 14q23-31. Stroke,37(4), 1021–1027. https://doi.org/10.1161/01.STR.0000206153.92675.b9.CrossRefPubMed

Paschoal, E. H. A., Yamaki, V. N., Teixeira, R. K. C., Paschoal Junior, F. M., Jong, A. L. G. S., Teixeira, M. J., et al. (2018). Relationship between endothelial nitric oxide synthase (eNOS) and natural history of intracranial aneurysms: Meta-analysis. Neurosurgical Review,41(1), 87–94. https://doi.org/10.1007/s10143-016-0761-4.CrossRefPubMed

Paterakis, K., Koutsias, S., Doxani, C., Xanthopoulou, P., Kokkali, C., Mpoulimari, I., et al. (2017). Variants of the elastin (ELN) gene and susceptibility to intracranial aneurysm: A synthesis of genetic association studies using a genetic model-free approach. International Journal of Neuroscience,127(7), 567–572. https://doi.org/10.1080/00207454.2016.1212027.CrossRefPubMed

Pentimalli, L., Modesti, A., Vignati, A., Marchese, E., Albanese, A., Di Rocco, F., et al. (2004). Role of apoptosis in intracranial aneurysm rupture. Journal of Neurosurgery,101(6), 1018–1025. https://doi.org/10.3171/jns.2004.101.6.1018.CrossRefPubMed

Pirson, Y. (2010). Extrarenal manifestations of autosomal dominant polycystic kidney disease. Advances in Chronic Kidney Disease,17(2), 173–180. https://doi.org/10.1053/j.ackd.2010.01.003.CrossRefPubMed

Rauch, A. (2011). The shortest of the short: Pericentrin mutations and beyond. Best Practice & Research Clinical Endocrinology & Metabolism,25(1), 125–130. https://doi.org/10.1016/j.beem.2010.10.015.CrossRef

Rauch, A., Thiel, C. T., Schindler, D., Wick, U., Crow, Y. J., Ekici, A. B., et al. (2008). Mutations in the pericentrin (PCNT) gene cause primordial dwarfism. Science,319(5864), 816–819. https://doi.org/10.1126/science.1151174.CrossRefPubMed

Ravindra, V. M., Karsy, M., Schmidt, R. H., Taussky, P., Park, M. S., & Bollo, R. J. (2016). Rapid de novo aneurysm formation after clipping of a ruptured middle cerebral artery aneurysm in an infant with an MYH11 mutation. Journal of Neurosurgery Pediatrics,18(4), 463–470. https://doi.org/10.3171/2016.5.PEDS16115.CrossRefPubMed

Rodrigues, V. J., Elsayed, S., Loeys, B. L., Dietz, H. C., & Yousem, D. M. (2009). Neuroradiologic manifestations of Loeys-Dietz syndrome type 1. AJNR American Journal of Neuroradiology,30(8), 1614–1619. https://doi.org/10.3174/ajnr.A1651.CrossRefPubMed

Ronkainen, A., Hernesniemi, J., Puranen, M., Niemitukia, L., Vanninen, R., Ryynanen, M., et al. (1997). Familial intracranial aneurysms. Lancet,349(9049), 380–384. https://doi.org/10.1016/S0140-6736(97)80009-8.CrossRefPubMed

Ronkainen, A., Hernesniemi, J., & Ryynanen, M. (1993). Familial subarachnoid hemorrhage in east Finland, 1977-1990. Neurosurgery,33(5), 787–796 (discussion 796–797).PubMed

Roos, Y. B., Pals, G., Struycken, P. M., Rinkel, G. J., Limburg, M., Pronk, J. C., et al. (2004). Genome-wide linkage in a large Dutch consanguineous family maps a locus for intracranial aneurysms to chromosome 2p13. Stroke,35(10), 2276–2281. https://doi.org/10.1161/01.STR.0000141415.28155.46.CrossRefPubMed

Roszer, T. (2015). Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators of Inflammation,2015, 816460. https://doi.org/10.1155/2015/816460.CrossRefPubMedPubMedCentral

Rui, Y. N., Xu, Z., Fang, X., Menezes, M. R., Balzeau, J., Niu, A., et al. (2017). The intracranial aneurysm gene THSD1 connects endosome dynamics to nascent focal adhesion assembly. Cellular Physiology and Biochemistry,43(6), 2200–2211. https://doi.org/10.1159/000484298.CrossRefPubMed

Ruigrok, Y. M., Rinkel, G. J., & Wijmenga, C. (2006). The versican gene and the risk of intracranial aneurysms. Stroke,37(9), 2372–2374. https://doi.org/10.1161/01.STR.0000236499.55301.09.CrossRefPubMed

Ruigrok, Y. M., Rinkel, G. J., Wijmenga, C., Kasuya, H., Tajima, A., Takahashi, T., et al. (2009). Association analysis of genes involved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort. Cerebrovascular Diseases,28(2), 131–134. https://doi.org/10.1159/000223438.CrossRefPubMed

Ruigrok, Y. M., Wijmenga, C., Rinkel, G. J., van’t Slot, R., Baas, F., Wolfs, M., et al. (2008). Genomewide linkage in a large Dutch family with intracranial aneurysms: replication of 2 loci for intracranial aneurysms to chromosome 1p36.11-p36.13 and Xp22.2-p22.32. Stroke, 39(4), 1096–1102. https://doi.org/10.1161/strokeaha.107.495168.CrossRef

Santiago-Sim, T., Depalma, S. R., Ju, K. L., McDonough, B., Seidman, C. E., Seidman, J. G., et al. (2009a). Genomewide linkage in a large Caucasian family maps a new locus for intracranial aneurysms to chromosome 13q. Stroke,40(3 Suppl), S57–60. https://doi.org/10.1161/STROKEAHA.108.534396.CrossRefPubMed

Santiago-Sim, T., Fang, X., Hennessy, M. L., Nalbach, S. V., DePalma, S. R., Lee, M. S., et al. (2016). THSD1 (thrombospondin type 1 domain containing protein 1) mutation in the pathogenesis of intracranial aneurysm and subarachnoid hemorrhage. Stroke,47(12), 3005–3013. https://doi.org/10.1161/STROKEAHA.116.014161.CrossRefPubMedPubMedCentral

Santiago-Sim, T., & Kim, D. H. (2011). Pathobiology of intracranial aneurysms. In H. R. Winn (Ed.), Youmans neurological surgery (6th ed., Vol. 4, pp. 3747–3755). Philadelphia, PA: Elsevier.CrossRef

Santiago-Sim, T., Mathew-Joseph, S., Pannu, H., Milewicz, D. M., Seidman, C. E., Seidman, J. G., et al. (2009b). Sequencing of TGF-beta pathway genes in familial cases of intracranial aneurysm. Stroke,40(5), 1604–1611. https://doi.org/10.1161/STROKEAHA.108.540245.CrossRefPubMedPubMedCentral

Santoro, M. M., Samuel, T., Mitchell, T., Reed, J. C., & Stainier, D. Y. (2007). Birc2 (cIap1) regulates endothelial cell integrity and blood vessel homeostasis. Nature Genetics,39(11), 1397–1402. https://doi.org/10.1038/ng.2007.8.CrossRefPubMed

Sathyan, S., Koshy, L. V., Balan, S., Easwer, H. V., Premkumar, S., Nair, S., et al. (2014). Association of Versican (VCAN) gene polymorphisms rs251124 and rs2287926 (G428D), with intracranial aneurysm. Meta Gene,2, 651–660. https://doi.org/10.1016/j.mgene.2014.07.001.CrossRefPubMedPubMedCentral

Sawyer, D. M., Pace, L. A., Pascale, C. L., Kutchin, A. C., O’Neill, B. E., Starke, R. M., et al. (2016). Lymphocytes influence intracranial aneurysm formation and rupture: Role of extracellular matrix remodeling and phenotypic modulation of vascular smooth muscle cells. Journal of Neuroinflammation,13(1), 185. https://doi.org/10.1186/s12974-016-0654-z.CrossRefPubMedPubMedCentral

Scanarini, M., Mingrino, S., Zuccarello, M., & Trincia, G. (1978). Scanning electron microscopy (s.e.m.) of biopsy specimens of ruptured intracranial saccular aneurysms. Acta Neuropathologica,44(2), 131–134.CrossRef

Schievink, W. I., Parisi, J. E., Piepgras, D. G., & Michels, V. V. (1997). Intracranial aneurysms in Marfan’s syndrome: An autopsy study. Neurosurgery,41(4), 866–870 (discussion 871).CrossRef

Schievink, W. I., Riedinger, M., & Maya, M. M. (2005). Frequency of incidental intracranial aneurysms in neurofibromatosis type 1. American Journal of Medical Genetics Part A,134A(1), 45–48. https://doi.org/10.1002/ajmg.a.30475.CrossRefPubMed

Schievink, W. I., Schaid, D. J., Michels, V. V., & Piepgras, D. G. (1995). Familial aneurysmal subarachnoid hemorrhage: A community-based study. Journal of Neurosurgery,83(3), 426–429. https://doi.org/10.3171/jns.1995.83.3.0426.CrossRefPubMed

Schievink, W. I., Schaid, D. J., Rogers, H. M., Piepgras, D. G., & Michels, V. V. (1994). On the inheritance of intracranial aneurysms. Stroke,25(10), 2028–2037.CrossRef

Schurmann, C., Gremse, F., Jo, H., Kiessling, F., & Brandes, R. P. (2015). Micro-CT technique is well suited for documentation of remodeling processes in murine carotid arteries. PLoS ONE,10(6), e0130374. https://doi.org/10.1371/journal.pone.0130374.CrossRefPubMedPubMedCentral

Sforza, D. M., Putman, C. M., & Cebral, J. R. (2009). Hemodynamics of cerebral aneurysms. Annual Review of Fluid Mechanics,41, 91–107. https://doi.org/10.1146/annurev.fluid.40.111406.102126.CrossRefPubMedPubMedCentral

Shao, L., Qin, X., Liu, J., Jian, Z., Xiong, X., & Liu, R. (2017). Macrophage polarization in cerebral aneurysm: Perspectives and potential targets. Journal of Immunology Research,2017, 8160589. https://doi.org/10.1155/2017/8160589.CrossRefPubMedPubMedCentral

Shen, T. L., Park, A. Y., Alcaraz, A., Peng, X., Jang, I., Koni, P., et al. (2005). Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. Journal of Cell Biology,169(6), 941–952. https://doi.org/10.1083/jcb.200411155.CrossRefPubMed

Signorelli, F., Sela, S., Gesualdo, L., Chevrel, S., Tollet, F., Pailler-Mattei, C., et al. (2018). Hemodynamic stress, inflammation, and intracranial aneurysm development and rupture: A systematic review. World Neurosurg,115, 234–244. https://doi.org/10.1016/j.wneu.2018.04.143.CrossRefPubMed

Sima, X., Sun, H., Zhou, P., & You, C. (2015). A potential polymorphism in the promoter of Let-7 is associated with an increased risk of intracranial aneurysm: A case-control study. Medicine (Baltimore),94(51), e2267. https://doi.org/10.1097/MD.0000000000002267.CrossRef

Song, Y., Liu, P., Li, Z., Shi, Y., Huang, J., Li, S., et al. (2018). The effect of myosin light chain kinase on the occurrence and development of intracranial aneurysm. Frontiers in Cellular Neuroscience,12, 416. https://doi.org/10.3389/fncel.2018.00416.CrossRefPubMedPubMedCentral

Starke, R. M., Chalouhi, N., Ding, D., Raper, D. M., McKisic, M. S., Owens, G. K., et al. (2014). Vascular smooth muscle cells in cerebral aneurysm pathogenesis. Translational Stroke Research,5(3), 338–346. https://doi.org/10.1007/s12975-013-0290-1.CrossRefPubMed

Stehbens, W. E., Delahunt, B., & Hilless, A. D. (1989). Early berry aneurysm formation in Marfan’s syndrome. Surgical Neurology,31(3), 200–202.CrossRef

Sun, H., Zhang, D., & Zhao, J. (2008). The interleukin-6 gene -572G > C promoter polymorphism is related to intracranial aneurysms in Chinese Han nationality. Neuroscience Letters,440(1), 1–3. https://doi.org/10.1016/j.neulet.2008.04.077.CrossRefPubMed

Suo, M., Lin, Y., Yu, H., Song, W., Sun, K., Song, Y., et al. (2014). Association of Kallikrein gene polymorphisms with sporadic intracranial aneurysms in the Chinese population. Journal of Neurosurgery,120(6), 1397–1401. https://doi.org/10.3171/2013.11.JNS131036.CrossRefPubMed

Superti-Furga, A., Gugler, E., Gitzelmann, R., & Steinmann, B. (1988). Ehlers-Danlos syndrome type IV: A multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen. Journal of Biological Chemistry,263(13), 6226–6232.PubMed

Tada, Y., Kanematsu, Y., Kanematsu, M., Nuki, Y., Liang, E. I., Wada, K., et al. (2011). A mouse model of intracranial aneurysm: Technical considerations. Acta Neurochirurgica. Supplementum,111, 31–35. https://doi.org/10.1007/978-3-7091-0693-8_6.CrossRef

Teasdale, G. M., Wardlaw, J. M., White, P. M., Murray, G., Teasdale, E. M., & Easton, V. (2005). The familial risk of subarachnoid haemorrhage. Brain,128(Pt 7), 1677–1685. https://doi.org/10.1093/brain/awh497.CrossRefPubMed

Teo, M., Johnson, J. N., Bell-Stephens, T. E., Marks, M. P., Do, H. M., Dodd, R. L., et al. (2016). Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies. Journal of Neurosurgery Pediatrics,25(6), 717–723. https://doi.org/10.3171/2016.6.PEDS16243.CrossRefPubMed

Thompson, B. G., Brown, R. D., Jr., Amin-Hanjani, S., Broderick, J. P., Cockroft, K. M., Connolly, E. S., Jr., et al. (2015). Guidelines for the management of patients with unruptured intracranial aneurysms: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke,46(8), 2368–2400. https://doi.org/10.1161/STR.0000000000000070.CrossRefPubMed

Tromp, G., Weinsheimer, S., Ronkainen, A., & Kuivaniemi, H. (2014). Molecular basis and genetic predisposition to intracranial aneurysm. Annals of Medicine,46(8), 597–606. https://doi.org/10.3109/07853890.2014.949299.CrossRefPubMedPubMedCentral

Tsipouras, P., Byers, P. H., Schwartz, R. C., Chu, M. L., Weil, D., Pepe, G., et al. (1986). Ehlers-Danlos syndrome type IV: Cosegregation of the phenotype to a COL3A1 allele of type III procollagen. Human Genetics,74(1), 41–46.CrossRef

van den Berg, J. S., Limburg, M., & Hennekam, R. C. (1996). Is Marfan syndrome associated with symptomatic intracranial aneurysms? Stroke,27(1), 10–12.CrossRef

van der Voet, M., Olson, J. M., Kuivaniemi, H., Dudek, D. M., Skunca, M., Ronkainen, A., et al. (2004). Intracranial aneurysms in Finnish families: confirmation of linkage and refinement of the interval to chromosome 19q13.3. The American Journal of Human Genetics, 74(3), 564–571. https://doi.org/10.1086/382285.CrossRef

Vanakker, O. M., Hemelsoet, D., & De Paepe, A. (2011). Hereditary connective tissue diseases in young adult stroke: a comprehensive synthesis. Stroke Research and Treatment,2011, 712903. https://doi.org/10.4061/2011/712903.CrossRefPubMedPubMedCentral

Verlaan, D. J., Dube, M. P., St-Onge, J., Noreau, A., Roussel, J., Satge, N., et al. (2006). A new locus for autosomal dominant intracranial aneurysm, ANIB4, maps to chromosome 5p15.2-14.3. Journal of Medical Genetics,43(6), e31. https://doi.org/10.1136/jmg.2005.033209.CrossRefPubMedPubMedCentral

Vo, A. H., Swaroop, A., Liu, Y., Norris, Z. G., & Shavit, J. A. (2013). Loss of fibrinogen in zebrafish results in symptoms consistent with human hypofibrinogenemia. PLoS ONE,8(9), e74682. https://doi.org/10.1371/journal.pone.0074682.CrossRefPubMedPubMedCentral

Wang, Q., Liu, Z., Ren, J., Morgan, S., Assa, C., & Liu, B. (2015a). Receptor-interacting protein kinase 3 contributes to abdominal aortic aneurysms via smooth muscle cell necrosis and inflammation. Circulation Research,116(4), 600–611. https://doi.org/10.1161/CIRCRESAHA.116.304899.CrossRefPubMedPubMedCentral

Wang, Y., Emeto, T. I., Lee, J., Marshman, L., Moran, C., Seto, S. W., et al. (2015b). Mouse models of intracranial aneurysm. Brain Pathology,25(3), 237–247. https://doi.org/10.1111/bpa.12175.CrossRefPubMed

Weinsheimer, S., Goddard, K. A., Parrado, A. R., Lu, Q., Sinha, M., Lebedeva, E. R., et al. (2007). Association of kallikrein gene polymorphisms with intracranial aneurysms. Stroke,38(10), 2670–2676. https://doi.org/10.1161/STROKEAHA.107.486225.CrossRefPubMed

Wiebers, D. O., Piepgras, D. G., Meyer, F. B., Kallmes, D. F., Meissner, I., Atkinson, J. L., et al. (2004). Pathogenesis, natural history, and treatment of unruptured intracranial aneurysms. Mayo Clinic Proceedings,79(12), 1572–1583. https://doi.org/10.4065/79.12.1572.CrossRefPubMed

Wiebers, D. O., Whisnant, J. P., Huston, J., 3rd, Meissner, I., Brown, R. D., Jr., Piepgras, D. G., et al. (2003). Unruptured intracranial aneurysms: Natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet,362(9378), 103–110.CrossRef

Willems, M., Genevieve, D., Borck, G., Baumann, C., Baujat, G., Bieth, E., et al. (2010). Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. Journal of Medical Genetics,47(12), 797–802. https://doi.org/10.1136/jmg.2009.067298.CrossRefPubMed

Williams, L. N., & Brown, R. D., Jr. (2013). Management of unruptured intracranial aneurysms. Neurology: Clinical Practice,3(2), 99–108. https://doi.org/10.1212/CPJ.0b013e31828d9f6b.CrossRef

Wozniak, M. A., Modzelewska, K., Kwong, L., & Keely, P. J. (2004). Focal adhesion regulation of cell behavior. Biochimica et Biophysica Acta,1692(2–3), 103–119. https://doi.org/10.1016/j.bbamcr.2004.04.007.CrossRefPubMed

Wu, Q., Zhang, J., Koh, W., Yu, Q., Zhu, X., Amsterdam, A., et al. (2015). Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in zebrafish. FASEB J,29(12), 4989–5005. https://doi.org/10.1096/fj.15-273409.CrossRefPubMedPubMedCentral

Wu, Y., Li, Z., Shi, Y., Chen, L., Tan, H., Wang, Z., et al. (2017). Exome sequencing identifies LOXL2 mutation as a cause of familial intracranial aneurysm. World Neurosurgery. https://doi.org/10.1016/j.wneu.2017.10.094.CrossRefPubMedPubMedCentral

Xu, Z., Rui, Y. N., Balzeau, J., Menezes, M. R., Niu, A., Hagan, J. P., et al. (2017). Highly efficient one-step scarless protein tagging by type IIS restriction endonuclease-mediated precision cloning. Biochemical and Biophysical Research Communications,490(1), 8–16. https://doi.org/10.1016/j.bbrc.2017.05.153.CrossRefPubMedPubMedCentral

Xu, Z., Rui, Y. N., Hagan, J. P., & Kim, D. H. (2018). Precision tagging: A novel seamless protein tagging by combinational use of Type II and Type IIS restriction endonucleases. Bio Protoc. https://doi.org/10.21769/bioprotoc.2721.CrossRefPubMedPubMedCentral

Yamada, S., Utsunomiya, M., Inoue, K., Nozaki, K., Inoue, S., Takenaka, K., et al. (2004). Genome-wide scan for Japanese familial intracranial aneurysms: Linkage to several chromosomal regions. Circulation,110(24), 3727–3733. https://doi.org/10.1161/01.CIR.0000143077.23367.18.CrossRefPubMed

Yan, J., Hitomi, T., Takenaka, K., Kato, M., Kobayashi, H., Okuda, H., et al. (2015). Genetic study of intracranial aneurysms. Stroke,46(3), 620–626. https://doi.org/10.1161/STROKEAHA.114.007286.CrossRefPubMed

Yang, X., Li, J., Fang, Y., Zhang, Z., Jin, D., Chen, X., et al. (2018). Rho guanine nucleotide exchange factor ARHGEF17 is a risk gene for intracranial aneurysms. Circulation: Genomic and Precision Medicine,11(7), e002099. https://doi.org/10.1161/CIRCGEN.117.002099.CrossRef

Yasuno, K., Bilguvar, K., Bijlenga, P., Low, S. K., Krischek, B., Auburger, G., et al. (2010). Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nature Genetics,42(5), 420–425. https://doi.org/10.1038/ng.563.CrossRefPubMedPubMedCentral

Zacharia, B. E., Hickman, Z. L., Grobelny, B. T., DeRosa, P., Kotchetkov, I., Ducruet, A. F., et al. (2010). Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurgery Clinics of North America,21(2), 221–233. https://doi.org/10.1016/j.nec.2009.10.002.CrossRefPubMed

Zhang, G., Tu, Y., Feng, W., Huang, L., Li, M., & Qi, S. (2011). Association of interleukin-6-572G/C gene polymorphisms in the Cantonese population with intracranial aneurysms. Journal of the Neurological Sciences,306(1–2), 94–97. https://doi.org/10.1016/j.jns.2011.03.036.CrossRefPubMed

Zhang, L. T., Wei, F. J., Zhao, Y., Zhang, Z., Dong, W. T., Jin, Z. N., et al. (2015). Intracranial aneurysm risk factor genes: Relationship with intracranial aneurysm risk in a Chinese Han population. Genetics and Molecular Research,14(2), 6865–6878. https://doi.org/10.4238/2015.June.18.30.CrossRefPubMed

Zheng, S., Su, A., Sun, H., & You, C. (2013). The association between interleukin-6 gene polymorphisms and intracranial aneurysms: A meta-analysis. Human Immunology,74(12), 1679–1683. https://doi.org/10.1016/j.humimm.2013.08.274.CrossRefPubMed

Zholdybayeva, E. V., Medetov, Y. Z., Aitkulova, A. M., Makhambetov, Y. T., Akshulakov, S. K., Kaliyev, A. B., et al. (2018). Genetic risk factors for intracranial aneurysm in the Kazakh population. Journal of Molecular Neuroscience,66(1), 135–145. https://doi.org/10.1007/s12031-018-1134-y.CrossRefPubMed

Zhou, S., Ambalavanan, A., Rochefort, D., Xie, P., Bourassa, C. V., Hince, P., et al. (2016). RNF213 is associated with intracranial aneurysms in the French-Canadian population. American Journal of Human Genetics,99(5), 1072–1085. https://doi.org/10.1016/j.ajhg.2016.09.001.CrossRefPubMedPubMedCentral

Zhou, S., Dion, P. A., & Rouleau, G. A. (2018). Genetics of intracranial aneurysms. Stroke,49(3), 780–787. https://doi.org/10.1161/STROKEAHA.117.018152.CrossRefPubMed

Titel: Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms
verfasst von: Zhen Xu
Yan-Ning Rui
John P. Hagan
Dong H. Kim
Publikationsdatum: 04.05.2019
Verlag: Springer US
Erschienen in: NeuroMolecular Medicine / Ausgabe 4/2019
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-019-08537-7

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Was nützt die Kraniektomie bei schwerer tiefer Hirnblutung?

17.05.2024 Hirnblutung Nachrichten

Eine Studie zum Nutzen der druckentlastenden Kraniektomie nach schwerer tiefer supratentorieller Hirnblutung deutet einen Nutzen der Operation an. Für überlebende Patienten ist das dennoch nur eine bedingt gute Nachricht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2019

Acid–Base and Electrolyte Changes Drive Early Pathology in Ischemic Stroke

Preserving Mitochondrial Structure and Motility Promotes Recovery of White Matter After Ischemia

Stroke: Molecular Mechanisms and Therapies

Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion

A Short Bout of Exercise Prior to Stroke Improves Functional Outcomes by Enhancing Angiogenesis