{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:47:38Z","timestamp":1783435658850,"version":"3.54.6"},"reference-count":195,"publisher":"Georg Thieme Verlag KG","issue":"02","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neurol Surg A Cent Eur Neurosurg"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intracranial aneurysms (IAs) are persistent, localized dilatations of the arterial wall that are found in \u223c3% of the general population. The most severe complication of IAs is rupture, which results in devastating consequences such as subarachnoid hemorrhage and brain damage with serious neurologic sequelae. Numerous studies have characterized the mechanisms underlying IA development and growth and identified several environmental modifiable (smoking, hypertension) and nonmodifiable risk factors (related to the histology of cerebral arteries and genetic factors) in its pathogenesis. Hemodynamic stress also likely plays a crucial role in the formation of IAs and is conditioned by the geometry and morphology of the vessel tree, but its role in the natural history of unruptured IAs remains poorly understood; it is believed that changes in blood flow might generate the hemodynamic forces that are responsible for damage to the vascular wall and vessel remodeling that lead to IA formation. This review summarizes the most relevant data on the current theories on the formation of IAs, with particular emphasis on the roles of special conditions resulting from the microscopic anatomy of intracranial arteries, hemodynamic factors, bifurcation morphometry, inflammatory pathways, and the genetic factors involved in IA formation.<\/jats:p>","DOI":"10.1055\/a-1994-8560","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T19:24:39Z","timestamp":1670527479000},"page":"125-141","source":"Crossref","is-referenced-by-count":5,"title":["Biology, Physics, and Genetics of Intracranial Aneurysm Formation: A Review"],"prefix":"10.1055","volume":"87","author":[{"given":"Karolina","family":"\u0106miel-Smorzyk","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Silesia, Sosnowiec, Silesia, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"\u0141adzi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Silesia, Sosnowiec, Silesia, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-3409","authenticated-orcid":false,"given":"Wojciech","family":"Kaspera","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical University of Silesia, Sosnowiec, Silesia, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"issue":"07","key":"ref1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S1474-4422(11)70109-0","article-title":"Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis","volume":"10","author":"M H Vlak","year":"2011","journal-title":"Lancet Neurol"},{"issue":"04","key":"ref2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.2174\/221155281120100005","article-title":"Intracranial non-traumatic aneurysms in children and adolescents","volume":"9","author":"A Sorteberg","year":"2013","journal-title":"Curr Pediatr Rev"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3171\/jns.2002.96.1.0043","article-title":"Prevalence of asymptomatic incidental aneurysms: review of 4568 arteriograms","volume":"96","author":"H R Winn","year":"2002","journal-title":"J Neurosurg"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3171\/jns.2002.96.1.0003","article-title":"Unruptured intracranial aneurysms: a review","volume":"96","author":"B Weir","year":"2002","journal-title":"J Neurosurg"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1161\/01.STR.29.1.251","article-title":"Prevalence and risk of rupture of intracranial aneurysms: a systematic review","volume":"29","author":"G J Rinkel","year":"1998","journal-title":"Stroke"},{"issue":"24","key":"ref6","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1056\/NEJM199812103392401","article-title":"Unruptured intracranial aneurysms: risk of rupture and risks of surgical intervention","volume":"339","author":"International Study of Unruptured Intracranial Aneurysms Investigators","year":"1998","journal-title":"N Engl J Med"},{"issue":"04","key":"ref7","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1161\/STROKEAHA.111.000329","article-title":"Independent risk factors for intracranial aneurysms and their joint effect: a case-control study","volume":"44","author":"M H Vlak","year":"2013","journal-title":"Stroke"},{"issue":"05","key":"ref8","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00701-017-3142-z","article-title":"Intracranial aneurysms in patients with autosomal dominant polycystic kidney disease: prevalence, risk of rupture, and management. A systematic review","volume":"159","author":"F Cagnazzo","year":"2017","journal-title":"Acta Neurochir (Wien)"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1161\/STROKEAHA.117.020342","article-title":"Risk factors for and clinical consequences of multiple intracranial aneurysms: a systematic review and meta-analysis","volume":"49","author":"R Jabbarli","year":"2018","journal-title":"Stroke"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"H189","DOI":"10.1152\/ajpheart.00087.2018","article-title":"Elastin, arterial mechanics, and cardiovascular disease","volume":"315","author":"A J Cocciolone","year":"2018","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"02","key":"ref11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s12975-013-0294-x","article-title":"Cerebral aneurysms: formation, progression, and developmental chronology","volume":"5","author":"N Etminan","year":"2014","journal-title":"Transl Stroke Res"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s00401-011-0939-3","article-title":"Saccular intracranial aneurysm: pathology and mechanisms","volume":"123","author":"J Fr\u00f6sen","year":"2012","journal-title":"Acta Neuropathol"},{"issue":"S 01","key":"ref13","doi-asserted-by":"crossref","first-page":"i58","DOI":"10.1136\/jnis.2009.002055.rep","article-title":"Inflammatory changes in the aneurysm wall: a review","volume":"10","author":"R Tulamo","year":"2018","journal-title":"J Neurointerv Surg"},{"issue":"09","key":"ref14","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1161\/01.STR.25.9.1799","article-title":"The layered fabric of cerebral artery fenestrations","volume":"25","author":"H M Finlay","year":"1994","journal-title":"Stroke"},{"issue":"06","key":"ref15","doi-asserted-by":"crossref","first-page":"666","DOI":"10.3171\/jns.1972.37.6.0666","article-title":"Physical factors in the initiation, growth, and rupture of human intracranial saccular aneurysms","volume":"37","author":"G G Ferguson","year":"1972","journal-title":"J Neurosurg"},{"key":"ref16","first-page":"239","article-title":"On the origin of miliary aneurysms of the superficial cerebral arteries","volume":"47","author":"W D Forbus","year":"1930","journal-title":"Bull Johns Hopkins Hosp"},{"issue":"02","key":"ref17","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/path.1700510206","article-title":"Medial defects in the circle of Willis and their relation to aneurysm formation","volume":"51","author":"L E Glynn","year":"1940","journal-title":"J Pathol Bacteriol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3171\/jns.1962.19.4.0337","article-title":"Medial defects in the meningeal arteries","volume":"19","author":"O Hassler","year":"1962","journal-title":"J Neurosurg"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1177\/000331976301400705","article-title":"Media defects in human arteries","volume":"14","author":"O Hassler","year":"1963","journal-title":"Angiology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/path.1700780119","article-title":"Medial defects of the cerebral arteries of man","volume":"78","author":"W E Stehbens","year":"1959","journal-title":"J Pathol Bacteriol"},{"issue":"4554","key":"ref21","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/179327a0","article-title":"Medial defects of the cerebral arteries of some mammals","volume":"179","author":"W E Stehbens","year":"1957","journal-title":"Nature"},{"key":"ref22","first-page":"667","volume-title":"Arterial structure at branches and bifurcations with reference to physiological and pathological processes, including aneurysm formation","author":"W E Stehbens","year":"1981"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1161\/01.STR.19.4.507","article-title":"Involvement of internal elastic lamina in development of induced cerebral aneurysms in rats","volume":"19","author":"C Kim","year":"1988","journal-title":"Stroke"},{"issue":"05","key":"ref24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0090-3019(92)90017-H","article-title":"Alterations in cerebral vessels in experimental animals and their possible relationship to the development of aneurysms","volume":"38","author":"C Kim","year":"1992","journal-title":"Surg Neurol"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/path.1700570308","article-title":"Gross defects in the muscular and elastic coats of the larger cerebral arteries","volume":"57","author":"R Carmichael","year":"1945","journal-title":"J Pathol Bacteriol"},{"issue":"01","key":"ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/path.1700620102","article-title":"The pathogenesis of noninflammatory cerebral aneurysms","volume":"62","author":"R Carmichael","year":"1950","journal-title":"J Pathol Bacteriol"},{"issue":"04","key":"ref27","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1136\/jnnp.22.4.259","article-title":"Some observations on the pathogenesis and natural history of intracranial aneurysms","volume":"22","author":"T Crawford","year":"1959","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3171\/jns.1963.20.1.0001","article-title":"Experimental carotid ligation followed by aneurysmal formation and other morphological changes in the circle of Willis","volume":"20","author":"O Hassler","year":"1963","journal-title":"J Neurosurg"},{"issue":"02","key":"ref29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0090-3019(97)00154-7","article-title":"Do cerebral aneurysms originate at the site of medial defects? Microscopic examinations of experimental aneurysms at the fenestration of the anterior cerebral artery in rats","volume":"50","author":"K Futami","year":"1998","journal-title":"Surg Neurol"},{"issue":"03","key":"ref30","first-page":"399","article-title":"Early changes of experimentally induced cerebral aneurysms in rats. Light-microscopic study","volume":"124","author":"F Hazama","year":"1986","journal-title":"Am J Pathol"},{"issue":"03","key":"ref31","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1161\/CIRCULATIONAHA.113.001444","article-title":"Role of fluid dynamics and inflammation in intracranial aneurysm formation","volume":"129","author":"A S Turjman","year":"2014","journal-title":"Circulation"},{"issue":"06","key":"ref32","doi-asserted-by":"crossref","first-page":"823","DOI":"10.3171\/jns.1989.70.6.0823","article-title":"Etiology of intracranial berry aneurysms","volume":"70","author":"W E Stehbens","year":"1989","journal-title":"J Neurosurg"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"E21","DOI":"10.3171\/2019.5.FOCUS19234","article-title":"Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms","volume":"47","author":"J Fr\u00f6sen","year":"2019","journal-title":"Neurosurg Focus"},{"issue":"04","key":"ref34","first-page":"793","article-title":"Cerebral arteriovenous malformations and associated aneurysms: analysis of 305 cases from a series of 662 patients","volume":"46","author":"H J Meisel","year":"2000","journal-title":"Neurosurgery"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1227\/00006123-198901000-00014","article-title":"De novo aneurysm formation following carotid ligation: case report and review of the literature","volume":"24","author":"G N Dyste","year":"1989","journal-title":"Neurosurgery"},{"issue":"06","key":"ref36","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1227\/01.NEU.0000186009.62401.3C","article-title":"Color Doppler sonographic evaluation of collateral circulation in patients with cerebral aneurysms and the occlusion of the brachiocephalic vessels","volume":"57","author":"W Kaspera","year":"2005","journal-title":"Neurosurgery"},{"issue":"10","key":"ref37","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1161\/STROKEAHA.114.006055","article-title":"Morphological, hemodynamic, and clinical independent risk factors for anterior communicating artery aneurysms","volume":"45","author":"W Kaspera","year":"2014","journal-title":"Stroke"},{"issue":"05","key":"ref38","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1161\/01.STR.15.5.846","article-title":"Cerebral aneurysms and variations in the circle of Willis","volume":"15","author":"K N Kayembe","year":"1984","journal-title":"Stroke"},{"key":"ref39","first-page":"45","article-title":"Aneurysms and anatomical variation of cerebral arteries","volume":"75","author":"W E Stehbens","year":"1963","journal-title":"Arch Pathol"},{"issue":"01","key":"ref40","first-page":"41","article-title":"Experimentally induced cerebral aneurysms in rats: part V. Relation of hemodynamics in the circle of Willis to formation of aneurysms","volume":"13","author":"N Hashimoto","year":"1980","journal-title":"Surg Neurol"},{"issue":"06","key":"ref41","doi-asserted-by":"crossref","first-page":"903","DOI":"10.3171\/jns.1987.67.6.0903","article-title":"Experimental induction of cerebral aneurysms in monkeys","volume":"67","author":"N Hashimoto","year":"1987","journal-title":"J Neurosurg"},{"key":"ref42","first-page":"1","article-title":"Pathophysiology of development and rupture of cerebral aneurysms","volume":"48","author":"H J Steiger","year":"1990","journal-title":"Acta Neurochir Suppl (Wien)"},{"key":"ref43","first-page":"1","article-title":"Morphological studies on the large cerebral arteries, with reference to the aetiology of subarachnoid haemorrhage","volume":"154","author":"O Hassler","year":"1961","journal-title":"Acta Psychiatr Scand Suppl"},{"issue":"03","key":"ref44","first-page":"181","article-title":"Flow in glass models of arterial bifurcations and berry aneurysms at low Reynolds numbers","volume":"60","author":"W E Stehbens","year":"1975","journal-title":"Q J Exp Physiol Cogn Med Sci"},{"issue":"1080","key":"ref45","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1098\/rspb.1974.0024","article-title":"Haemodynamic production of lipid deposition, intimal teats, mural dissection and thrombosis in the blood vessel wall","volume":"185","author":"W E Stehbens","year":"1974","journal-title":"Proc R Soc Lond B Biol Sci"},{"issue":"03","key":"ref46","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1161\/01.STR.3.3.255","article-title":"The hemodynamic importance of the geometry of bifurcations in the circle of Willis (glass model studies)","volume":"3","author":"M R Roach","year":"1972","journal-title":"Stroke"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1161\/01.STR.27.11.2086","article-title":"Hemodynamic study of the anterior communicating artery","volume":"27","author":"H Ujiie","year":"1996","journal-title":"Stroke"},{"issue":"05","key":"ref48","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1227\/01.NEU.0000245599.92322.53","article-title":"A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo","volume":"59","author":"H Meng","year":"2006","journal-title":"Neurosurgery"},{"issue":"06","key":"ref49","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1161\/STROKEAHA.106.481234","article-title":"Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation","volume":"38","author":"H Meng","year":"2007","journal-title":"Stroke"},{"issue":"02","key":"ref50","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3171\/jns.1991.74.2.0258","article-title":"Cerebral blood flow patterns at major vessel bifurcations and aneurysms in rats","volume":"74","author":"H Nakatani","year":"1991","journal-title":"J Neurosurg"},{"issue":"04","key":"ref51","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/RCT.0b013e3182574dea","article-title":"Contribution of the hemodynamics of A1 dysplasia or hypoplasia to anterior communicating artery aneurysms: a 3-dimensional numerical simulation study","volume":"36","author":"L Xu","year":"2012","journal-title":"J Comput Assist Tomogr"},{"issue":"11","key":"ref52","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1161\/01.STR.0000144648.89172.0f","article-title":"Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamic study of 20 middle cerebral artery aneurysms","volume":"35","author":"M Shojima","year":"2004","journal-title":"Stroke"},{"issue":"07","key":"ref53","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1161\/STROKEAHA.107.509422","article-title":"Nascent aneurysm formation at the basilar terminus induced by hemodynamics","volume":"39","author":"L Gao","year":"2008","journal-title":"Stroke"},{"issue":"06","key":"ref54","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1007\/s10439-011-0267-8","article-title":"High fluid shear stress and spatial shear stress gradients affect endothelial proliferation, survival, and alignment","volume":"39","author":"J M Dolan","year":"2011","journal-title":"Ann Biomed Eng"},{"issue":"08","key":"ref55","doi-asserted-by":"crossref","first-page":"C1109","DOI":"10.1152\/ajpcell.00369.2011","article-title":"Endothelial cells express a unique transcriptional profile under very high wall shear stress known to induce expansive arterial remodeling","volume":"302","author":"J M Dolan","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"issue":"03","key":"ref56","doi-asserted-by":"crossref","first-page":"587","DOI":"10.3174\/ajnr.A2339","article-title":"Hemodynamics of cerebral aneurysm initiation: the role of wall shear stress and spatial wall shear stress gradient","volume":"32","author":"Z Kulcs\u00e1r","year":"2011","journal-title":"AJNR Am J Neuroradiol"},{"issue":"01","key":"ref57","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10237-016-0804-3","article-title":"Wall shear stress at the initiation site of cerebral aneurysms","volume":"16","author":"A J Geers","year":"2017","journal-title":"Biomech Model Mechanobiol"},{"issue":"12","key":"ref58","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1007\/s10439-009-9794-y","article-title":"Wall shear stress and pressure distribution on aneurysms and infundibulae in the posterior communicating artery bifurcation","volume":"37","author":"H Baek","year":"2009","journal-title":"Ann Biomed Eng"},{"issue":"04","key":"ref59","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.clineuro.2009.12.018","article-title":"Effects of smoking and hypertension on wall shear stress and oscillatory shear index at the site of intracranial aneurysm formation","volume":"112","author":"P K Singh","year":"2010","journal-title":"Clin Neurol Neurosurg"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/1471-2377-13-166","article-title":"New method for retrospective study of hemodynamic changes before and after aneurysm formation in patients with ruptured or unruptured aneurysms","volume":"13","author":"W J Le","year":"2013","journal-title":"BMC Neurol"},{"issue":"04","key":"ref61","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jbiomech.2008.10.006","article-title":"Can temporal fluctuation in spatial wall shear stress gradient initiate a cerebral aneurysm? A proposed novel hemodynamic index, the gradient oscillatory number (GON)","volume":"42","author":"Y Shimogonya","year":"2009","journal-title":"J Biomech"},{"issue":"05","key":"ref62","first-page":"1113","article-title":"Hemodynamics in a cerebral artery before and after the formation of an aneurysm","volume":"27","author":"A Mantha","year":"2006","journal-title":"AJNR Am J Neuroradiol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1259\/bjr\/67593727","article-title":"An objective approach to digital removal of saccular aneurysms: technique and applications","volume":"82","author":"M D Ford","year":"2009","journal-title":"Br J Radiol"},{"issue":"07","key":"ref64","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1007\/s10439-013-0794-6","article-title":"Investigating the influence of haemodynamic stimuli on intracranial aneurysm inception","volume":"41","author":"H Chen","year":"2013","journal-title":"Ann Biomed Eng"},{"issue":"03","key":"ref65","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1161\/01.ATV.5.3.293","article-title":"Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress","volume":"5","author":"D N Ku","year":"1985","journal-title":"Arteriosclerosis"},{"issue":"02","key":"ref66","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3171\/2018.3.JNS173128","article-title":"Induction of aneurysmogenic high positive wall shear stress gradient by wide angle at cerebral bifurcations, independent of flow rate","volume":"131","author":"A Lauric","year":"2018","journal-title":"J Neurosurg"},{"issue":"06","key":"ref67","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.3171\/2014.8.JNS1447","article-title":"Widening of the basilar bifurcation angle: association with presence of intracranial aneurysm, age, and female sex","volume":"121","author":"F T\u00fct\u00fcnc\u00fc","year":"2014","journal-title":"J Neurosurg"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"e379","DOI":"10.1016\/j.wneu.2018.09.112","article-title":"The optimality principle decreases hemodynamic stresses for aneurysm initiation at anterior cerebral artery bifurcations","volume":"121","author":"X J Zhang","year":"2019","journal-title":"World Neurosurg"},{"issue":"06","key":"ref69","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1227\/NEU.0000000000000713","article-title":"Morphological parameters associated with middle cerebral artery aneurysms","volume":"76","author":"A Can","year":"2015","journal-title":"Neurosurgery"},{"issue":"01","key":"ref70","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1227\/NEU.0000000000000564","article-title":"Effect of vascular anatomy on the formation of basilar tip aneurysms","volume":"76","author":"A Can","year":"2015","journal-title":"Neurosurgery"},{"issue":"05","key":"ref71","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.wneu.2015.05.078","article-title":"Association between vascular anatomy and posterior communicating artery aneurysms","volume":"84","author":"A Can","year":"2015","journal-title":"World Neurosurg"},{"issue":"01","key":"ref72","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1038\/s41598-019-56061-2","article-title":"Morphological and hemodynamic risk factors for middle cerebral artery aneurysm: a case-control study of 190 patients","volume":"10","author":"W Kaspera","year":"2020","journal-title":"Sci Rep"},{"issue":"09","key":"ref73","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1212\/01.wnl.0000302176.03551.35","article-title":"Configuration of intracranial arteries and development of aneurysms: a follow-up study","volume":"70","author":"A S Bor","year":"2008","journal-title":"Neurology"},{"issue":"01","key":"ref74","doi-asserted-by":"crossref","first-page":"15255","DOI":"10.1038\/s41598-019-51734-4","article-title":"Asymmetrical middle cerebral artery bifurcations are more vulnerable to aneurysm formation","volume":"9","author":"X J Zhang","year":"2019","journal-title":"Sci Rep"},{"issue":"01","key":"ref75","doi-asserted-by":"crossref","first-page":"17144","DOI":"10.1038\/s41598-019-53715-z","article-title":"Asymmetrical than symmetrical cerebral arterial bifurcations are more vulnerable to aneurysm presence","volume":"9","author":"X J Zhang","year":"2019","journal-title":"Sci Rep"},{"issue":"03","key":"ref76","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10143-013-0450-5","article-title":"Differences between middle cerebral artery bifurcations with normal anatomy and those with aneurysms","volume":"36","author":"T Sadatomo","year":"2013","journal-title":"Neurosurg Rev"},{"issue":"13","key":"ref77","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1016\/j.jbiomech.2014.08.012","article-title":"Deviation from optimal vascular caliber control at middle cerebral artery bifurcations harboring aneurysms","volume":"47","author":"M I Baharoglu","year":"2014","journal-title":"J Biomech"},{"issue":"03","key":"ref78","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1073\/pnas.12.3.207","article-title":"The physiological principle of minimum work: I. The vascular system and the cost of blood volume","volume":"12","author":"C D Murray","year":"1926","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"06","key":"ref79","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1085\/jgp.9.6.835","article-title":"The physiological principle of minimum work applied to the angle of branching of arteries","volume":"9","author":"C D Murray","year":"1926","journal-title":"J Gen Physiol"},{"issue":"06","key":"ref80","doi-asserted-by":"crossref","first-page":"711","DOI":"10.3109\/02841859809175503","article-title":"Shear stress in cerebral arteries carrying saccular aneurysms. A preliminary study","volume":"39","author":"S Rossitti","year":"1998","journal-title":"Acta Radiol"},{"issue":"06","key":"ref81","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1161\/01.RES.38.6.572","article-title":"Vessel caliber and branch-angle of human coronary artery branch-points","volume":"38","author":"G M Hutchins","year":"1976","journal-title":"Circ Res"},{"issue":"06","key":"ref82","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1139\/y86-109","article-title":"Branching characteristics of human coronary arteries","volume":"64","author":"M Zamir","year":"1986","journal-title":"Can J Physiol Pharmacol"},{"issue":"03","key":"ref83","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1161\/01.STR.24.3.371","article-title":"Vascular dimensions of the cerebral arteries follow the principle of minimum work","volume":"24","author":"S Rossitti","year":"1993","journal-title":"Stroke"},{"issue":"01","key":"ref84","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3171\/jns.2004.101.1.0108","article-title":"Bifurcation geometry and the presence of cerebral artery aneurysms","volume":"101","author":"T Ingebrigtsen","year":"2004","journal-title":"J Neurosurg"},{"issue":"01","key":"ref85","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0022-5193(86)80021-2","article-title":"Cost analysis of arterial branching in the cardiovascular systems of man and animals","volume":"120","author":"M Zamir","year":"1986","journal-title":"J Theor Biol"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"e783","DOI":"10.1016\/j.wneu.2018.08.167","article-title":"Enlarged anterior cerebral artery bifurcation angles may induce abnormally enhanced hemodynamic stresses to initiate aneurysms","volume":"120","author":"X J Zhang","year":"2018","journal-title":"World Neurosurg"},{"issue":"01","key":"ref87","first-page":"89","article-title":"Angles between A1 and A2 segments of the anterior cerebral artery visualized by three-dimensional computed tomographic angiography and association of anterior communicating artery aneurysms","volume":"45","author":"H Kasuya","year":"1999","journal-title":"Neurosurgery"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jns.2017.01.062","article-title":"Relationship of the angle between the A1 and A2 segments of the anterior cerebral artery with formation and rupture of anterior communicating artery aneurysm","volume":"375","author":"J Ye","year":"2017","journal-title":"J Neurol Sci"},{"issue":"02","key":"ref89","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1161\/STROKEAHA.117.019701","article-title":"Presence of anterior communicating artery aneurysm is associated with age, bifurcation angle, and vessel diameter","volume":"49","author":"X J Zhang","year":"2018","journal-title":"Stroke"},{"issue":"06","key":"ref90","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1161\/STROKEAHA.118.020829","article-title":"Association of basilar bifurcation aneurysms with age, sex, and bifurcation geometry","volume":"49","author":"X J Zhang","year":"2018","journal-title":"Stroke"},{"issue":"09","key":"ref91","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1161\/STROKEAHA.114.005393","article-title":"Widening and high inclination of the middle cerebral artery bifurcation are associated with presence of aneurysms","volume":"45","author":"M I Baharoglu","year":"2014","journal-title":"Stroke"},{"issue":"07","key":"ref92","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s10439-012-0695-0","article-title":"High wall shear stress and spatial gradients in vascular pathology: a review","volume":"41","author":"J M Dolan","year":"2013","journal-title":"Ann Biomed Eng"},{"issue":"S 01","key":"ref93","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1097\/00005344-199321001-00002","article-title":"Hemodynamics and vascular endothelial biology","volume":"21","author":"R M Nerem","year":"1993","journal-title":"J Cardiovasc Pharmacol"},{"issue":"7057","key":"ref94","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nature03952","article-title":"A mechanosensory complex that mediates the endothelial cell response to fluid shear stress","volume":"437","author":"E Tzima","year":"2005","journal-title":"Nature"},{"issue":"08","key":"ref95","doi-asserted-by":"crossref","first-page":"C854","DOI":"10.1152\/ajpcell.00315.2012","article-title":"Differential gene expression by endothelial cells under positive and negative streamwise gradients of high wall shear stress","volume":"305","author":"J M Dolan","year":"2013","journal-title":"Am J Physiol Cell Physiol"},{"issue":"02","key":"ref96","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/00041433-200004000-00010","article-title":"Signalling pathways in vascular endothelium activated by shear stress: relevance to atherosclerosis","volume":"11","author":"N Resnick","year":"2000","journal-title":"Curr Opin Lipidol"},{"issue":"03","key":"ref97","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0079-6107(02)00052-4","article-title":"Fluid shear stress and the vascular endothelium: for better and for worse","volume":"81","author":"N Resnick","year":"2003","journal-title":"Prog Biophys Mol Biol"},{"issue":"04","key":"ref98","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s12017-019-08537-7","article-title":"Intracranial aneurysms: pathology, genetics, and molecular mechanisms","volume":"21","author":"Z Xu","year":"2019","journal-title":"Neuromolecular Med"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.HYP.31.1.162","article-title":"Effects of mechanical forces on signal transduction and gene expression in endothelial cells","volume":"31","author":"S Chien","year":"1998","journal-title":"Hypertension"},{"issue":"21","key":"ref100","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1001\/jama.282.21.2035","article-title":"Hemodynamic shear stress and its role in atherosclerosis","volume":"282","author":"A M Malek","year":"1999","journal-title":"JAMA"},{"issue":"06","key":"ref101","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.3171\/2009.10.JNS09759","article-title":"The critical role of hemodynamics in the development of cerebral vascular disease","volume":"112","author":"A M Nixon","year":"2010","journal-title":"J Neurosurg"},{"issue":"05","key":"ref102","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/01.ATV.18.5.677","article-title":"Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force","volume":"18","author":"O Traub","year":"1998","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"05","key":"ref103","first-page":"595","article-title":"Gene expression profile of the intima and media of experimentally induced cerebral aneurysms in rats by laser-microdissection and microarray techniques","volume":"22","author":"T Aoki","year":"2008","journal-title":"Int J Mol Med"},{"issue":"03","key":"ref104","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s12975-014-0340-3","article-title":"Smooth muscle cells and the formation, degeneration, and rupture of saccular intracranial aneurysm wall\u2013a review of current pathophysiological knowledge","volume":"5","author":"J Fr\u00f6sen","year":"2014","journal-title":"Transl Stroke Res"},{"issue":"03","key":"ref105","doi-asserted-by":"crossref","first-page":"214","DOI":"10.2176\/nmc.ra.2014-0337","article-title":"Molecular mechanisms of the formation and progression of intracranial aneurysms","volume":"55","author":"H Kataoka","year":"2015","journal-title":"Neurol Med Chir (Tokyo)"},{"issue":"04","key":"ref106","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.3390\/ijms19041245","article-title":"NF-\u03baB-mediated inflammation in the pathogenesis of intracranial aneurysm and subarachnoid hemorrhage. Does autophagy play a role?","volume":"19","author":"E Pawlowska","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"10","key":"ref107","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1161\/01.STR.0000140636.30204.da","article-title":"Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases","volume":"35","author":"J Fr\u00f6sen","year":"2004","journal-title":"Stroke"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4103\/2347-8659.154885","article-title":"Hemodynamics, inflammation, vascular remodeling, and the development and rupture of intracranial aneurysms: a review","volume":"2","author":"F Signorelli","year":"2015","journal-title":"Neuroimmunol Neuroinflamm"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.wneu.2018.04.143","article-title":"Hemodynamic stress, inflammation, and intracranial aneurysm development and rupture: a systematic review","volume":"115","author":"F Signorelli","year":"2018","journal-title":"World Neurosurg"},{"issue":"05","key":"ref110","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/00006123-199911000-00024","article-title":"Inflammation and intracranial aneurysms","volume":"45","author":"D Chyatte","year":"1999","journal-title":"Neurosurgery"},{"key":"ref111","first-page":"535921","article-title":"The development and the use of experimental animal models to study the underlying mechanisms of CA formation","volume":"2011","author":"T Aoki","year":"2011","journal-title":"J Biomed Biotechnol"},{"issue":"03","key":"ref112","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1161\/STROKEAHA.108.532556","article-title":"Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation","volume":"40","author":"T Aoki","year":"2009","journal-title":"Stroke"},{"issue":"01","key":"ref113","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.STR.0000252129.18605.c8","article-title":"Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats","volume":"38","author":"T Aoki","year":"2007","journal-title":"Stroke"},{"issue":"24","key":"ref114","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1161\/CIRCULATIONAHA.107.728303","article-title":"NF-kappaB is a key mediator of cerebral aneurysm formation","volume":"116","author":"T Aoki","year":"2007","journal-title":"Circulation"},{"issue":"04","key":"ref115","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/labinvest.2010.204","article-title":"Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS","volume":"91","author":"T Aoki","year":"2011","journal-title":"Lab Invest"},{"issue":"02","key":"ref116","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3171\/JNS-07\/08\/0405","article-title":"Endothelial injury and inflammatory response induced by hemodynamic changes preceding intracranial aneurysm formation: experimental study in rats","volume":"107","author":"M A Jamous","year":"2007","journal-title":"J Neurosurg"},{"issue":"01","key":"ref117","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/STROKEAHA.110.590976","article-title":"Critical roles of macrophages in the formation of intracranial aneurysm","volume":"42","author":"Y Kanematsu","year":"2011","journal-title":"Stroke"},{"issue":"07","key":"ref118","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1161\/STROKEAHA.119.025245","article-title":"Vessel wall imaging of evolving unruptured intracranial aneurysms","volume":"50","author":"T Matsushige","year":"2019","journal-title":"Stroke"},{"issue":"04","key":"ref119","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.3171\/2018.5.JNS18322","article-title":"Circumferential wall enhancement in evolving intracranial aneurysms on magnetic resonance vessel wall imaging","volume":"31","author":"S Omodaka","year":"2018","journal-title":"J Neurosurg"},{"issue":"07","key":"ref120","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2176\/nmc.st.2019-0034","article-title":"Macrophage imaging of intracranial aneurysms","volume":"59","author":"K Shimizu","year":"2019","journal-title":"Neurol Med Chir (Tokyo)"},{"issue":"08","key":"ref121","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.3174\/ajnr.A1125","article-title":"Gene expression profiling of experimental saccular aneurysms using deoxyribonucleic acid microarrays","volume":"29","author":"R Kadirvel","year":"2008","journal-title":"AJNR Am J Neuroradiol"},{"issue":"01","key":"ref122","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1161\/01.ATV.0000106321.63667.24","article-title":"Shear stress increases ICAM-1 and decreases VCAM-1 and E-selectin expressions induced by tumor necrosis factor-[alpha] in endothelial cells","volume":"24","author":"J J Chiu","year":"2004","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref123","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/CS20080196","article-title":"Role of TNF-alpha in vascular dysfunction","volume":"116","author":"H Zhang","year":"2009","journal-title":"Clin Sci (Lond)"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/2051-5960-2-34","article-title":"Critical role of TNF-alpha-TNFR1 signaling in intracranial aneurysm formation","volume":"2","author":"T Aoki","year":"2014","journal-title":"Acta Neuropathol Commun"},{"issue":"10","key":"ref125","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/jcbfm.2013.109","article-title":"TNF-\u03b1 induces phenotypic modulation in cerebral vascular smooth muscle cells: implications for cerebral aneurysm pathology","volume":"33","author":"M S Ali","year":"2013","journal-title":"J Cereb Blood Flow Metab"},{"issue":"6423","key":"ref126","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/362801a0","article-title":"The pathogenesis of atherosclerosis: a perspective for the 1990s","volume":"362","author":"R Ross","year":"1993","journal-title":"Nature"},{"issue":"04","key":"ref127","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3171\/2009.9.JNS09329","article-title":"Toll-like receptor 4 expression during cerebral aneurysm formation. Laboratory investigation","volume":"113","author":"T Aoki","year":"2010","journal-title":"J Neurosurg"},{"issue":"07","key":"ref128","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1161\/ATVBAHA.108.180760","article-title":"Reduced collagen biosynthesis is the hallmark of cerebral aneurysm: contribution of interleukin-1beta and nuclear factor-kappaB","volume":"29","author":"T Aoki","year":"2009","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"02","key":"ref129","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1161\/ATVBAHA.112.300432","article-title":"Genetic and pharmacologic disruption of interleukin-1\u03b2 signaling inhibits experimental aortic aneurysm formation","volume":"33","author":"W F Johnston","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref130","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1161\/01.STR.0000204028.39783.d9","article-title":"Impaired progression of cerebral aneurysms in interleukin-1beta-deficient mice","volume":"37","author":"T Moriwaki","year":"2006","journal-title":"Stroke"},{"issue":"09","key":"ref131","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1161\/STROKEAHA.117.017305","article-title":"Vascular tissue-type plasminogen activator promotes intracranial aneurysm formation","volume":"48","author":"P E Labeyrie","year":"2017","journal-title":"Stroke"},{"issue":"06","key":"ref132","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1111\/j.1476-5381.2011.01358.x","article-title":"PGE(2) -EP(2) signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-\u03baB","volume":"163","author":"T Aoki","year":"2011","journal-title":"Br J Pharmacol"},{"issue":"05","key":"ref133","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1161\/01.ATV.0000015078.09208.92","article-title":"Role of nuclear factor-kappa B activation in metalloproteinase-1, -3, and -9 secretion by human macrophages in vitro and rabbit foam cells produced in vivo","volume":"22","author":"A J Chase","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"10","key":"ref134","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1096\/fasebj.9.10.7542214","article-title":"Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers","volume":"9","author":"T Collins","year":"1995","journal-title":"FASEB J"},{"issue":"01","key":"ref135","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1182\/blood.V97.1.46","article-title":"Multiple signaling pathways regulate NF-kappaB-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells","volume":"97","author":"M Goebeler","year":"2001","journal-title":"Blood"},{"issue":"06","key":"ref136","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1084\/jem.177.6.1779","article-title":"Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide","volume":"177","author":"Q W Xie","year":"1993","journal-title":"J Exp Med"},{"issue":"08","key":"ref137","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1096\/fj.201701536R","article-title":"Endothelial microRNAs regulating the NF-\u03baB pathway and cell adhesion molecules during inflammation","volume":"32","author":"L Zhong","year":"2018","journal-title":"FASEB J"},{"issue":"03","key":"ref138","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s100169900052","article-title":"The role of nitric oxide in vascular biology and pathobiology","volume":"11","author":"J B Dattilo","year":"1997","journal-title":"Ann Vasc Surg"},{"issue":"10","key":"ref139","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1046\/j.1538-7836.2003.00345.x","article-title":"Nitric oxide in vascular biology","volume":"1","author":"G Walford","year":"2003","journal-title":"J Thromb Haemost"},{"key":"ref140","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.med.47.1.365","article-title":"The vascular biology of nitric oxide and its role in atherogenesis","volume":"47","author":"D M Lloyd-Jones","year":"1996","journal-title":"Annu Rev Med"},{"issue":"21","key":"ref141","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1161\/01.CIR.101.21.2532","article-title":"Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase","volume":"101","author":"S Fukuda","year":"2000","journal-title":"Circulation"},{"issue":"01","key":"ref142","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1227\/01.NEU.0000343541.85713.01","article-title":"Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation","volume":"65","author":"Z Wang","year":"2009","journal-title":"Neurosurgery"},{"issue":"03","key":"ref143","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0008-6363(99)00115-7","article-title":"Enzymatic function of nitric oxide synthases","volume":"43","author":"P J Andrew","year":"1999","journal-title":"Cardiovasc Res"},{"issue":"06","key":"ref144","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1253\/circj.CJ-09-0208","article-title":"Nitric oxide synthases and cardiovascular diseases: insights from genetically modified mice","volume":"73","author":"M Tsutsui","year":"2009","journal-title":"Circ J"},{"issue":"06","key":"ref145","doi-asserted-by":"crossref","first-page":"C1880","DOI":"10.1152\/ajpcell.2000.279.6.C1880","article-title":"Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress","volume":"279","author":"W Gosgnach","year":"2000","journal-title":"Am J Physiol Cell Physiol"},{"issue":"09","key":"ref146","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1161\/hq0901.095750","article-title":"Experimental abdominal aortic aneurysms in mice lacking expression of inducible nitric oxide synthase","volume":"21","author":"J K Lee","year":"2001","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"12","key":"ref147","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1161\/01.STR.0000102556.55600.3B","article-title":"Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms","volume":"34","author":"N Sadamasa","year":"2003","journal-title":"Stroke"},{"issue":"10","key":"ref148","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1161\/01.ATV.0000033517.48444.1A","article-title":"Human macrophage-induced vascular smooth muscle cell apoptosis requires NO enhancement of Fas\/Fas-L interactions","volume":"22","author":"J J Boyle","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"09","key":"ref149","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1097\/HJH;0b013e32833c2273","article-title":"Reduction of endothelial tight junction proteins is related to cerebral aneurysm formation in rats","volume":"28","author":"Y Tada","year":"2010","journal-title":"J Hypertens"},{"issue":"10","key":"ref150","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nrneph.2015.128","article-title":"Vascular complications in autosomal dominant polycystic kidney disease","volume":"11","author":"R D Perrone","year":"2015","journal-title":"Nat Rev Nephrol"},{"issue":"01","key":"ref151","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s10020-020-00246-3","article-title":"Autosomal dominant polycystic kidney disease and pioglitazone for its therapy: a comprehensive review with an emphasis on the molecular pathogenesis and pharmacological aspects","volume":"26","author":"A K Saini","year":"2020","journal-title":"Mol Med"},{"issue":"03","key":"ref152","first-page":"105","article-title":"Intracranial aneurysm formation in siblings with pseudoxanthoma elasticum: case report","volume":"54","author":"A Defillo","year":"2010","journal-title":"J Neurosurg Sci"},{"issue":"03","key":"ref153","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3171\/jns.1976.45.3.0342","article-title":"Giant intracranial aneurysm associated with Marfan's syndrome. Case report","volume":"45","author":"L H Finney","year":"1976","journal-title":"J Neurosurg"},{"issue":"05","key":"ref154","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1136\/jnnp.54.5.471-a","article-title":"Giant intracranial aneurysm associated with Marfan's syndrome: a case report","volume":"54","author":"P J Hainsworth","year":"1991","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"01","key":"ref155","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/00006123-199607000-00037","article-title":"Transcranial Doppler sonography in a patient with Ehlers-Danlos syndrome: case report","volume":"39","author":"M Holzschuh","year":"1996","journal-title":"Neurosurgery"},{"issue":"04","key":"ref156","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/00006123-199710000-00019","article-title":"Intracranial aneurysms in Marfan's syndrome: an autopsy study","volume":"41","author":"W I Schievink","year":"1997","journal-title":"Neurosurgery"},{"issue":"01","key":"ref157","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1161\/01.STR.27.1.10","article-title":"Is Marfan syndrome associated with symptomatic intracranial aneurysms?","volume":"27","author":"J S van den Berg","year":"1996","journal-title":"Stroke"},{"issue":"04","key":"ref158","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1159\/000016076","article-title":"Prevalence of symptomatic intracranial aneurysm and ischaemic stroke in pseudoxanthoma elasticum","volume":"10","author":"J S van den Berg","year":"2000","journal-title":"Cerebrovasc Dis"},{"issue":"08","key":"ref159","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1161\/01.STR.30.8.1632","article-title":"Marfan syndrome is not associated with intracranial aneurysms","volume":"30","author":"J E Conway","year":"1999","journal-title":"Stroke"},{"issue":"9049","key":"ref160","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S0140-6736(97)80009-8","article-title":"Familial intracranial aneurysms","volume":"349","author":"A Ronkainen","year":"1997","journal-title":"Lancet"},{"issue":"02","key":"ref161","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1161\/01.STR.29.2.359","article-title":"Risk of harboring an unruptured intracranial aneurysm","volume":"29","author":"A Ronkainen","year":"1998","journal-title":"Stroke"},{"issue":"03","key":"ref162","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1161\/01.STR.0000117966.47696.3A","article-title":"Familial intracranial aneurysms","volume":"35","author":"Y M Ruigrok","year":"2004","journal-title":"Stroke"},{"issue":"03","key":"ref163","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1161\/STROKEAHA.117.018152","article-title":"Genetics of intracranial aneurysms","volume":"49","author":"S Zhou","year":"2018","journal-title":"Stroke"},{"issue":"12","key":"ref164","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1161\/STROKEAHA.108.516948","article-title":"Differences in aneurysm and patient characteristics between cohorts of Finnish and Dutch patients with subarachnoid hemorrhage: time trends between 1986 and 2005","volume":"39","author":"C E van Munster","year":"2008","journal-title":"Stroke"},{"issue":"01","key":"ref165","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10897-016-0029-8","article-title":"A review of the genetics of intracranial berry aneurysms and implications for genetic counseling","volume":"26","author":"E Hitchcock","year":"2017","journal-title":"J Genet Couns"},{"key":"ref166","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1471-2350-10-3","article-title":"Genome screen in familial intracranial aneurysm","volume":"10","author":"T Foroud","year":"2009","journal-title":"BMC Med Genet"},{"issue":"01","key":"ref167","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1086\/426953","article-title":"Mapping a Mendelian form of intracranial aneurysm to 1p34.3-p36.13","volume":"76","author":"B V Nahed","year":"2005","journal-title":"Am J Hum Genet"},{"issue":"04","key":"ref168","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1086\/323614","article-title":"Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11","volume":"69","author":"H Onda","year":"2001","journal-title":"Am J Hum Genet"},{"issue":"24","key":"ref169","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1161\/01.CIR.0000143077.23367.18","article-title":"Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several chromosomal regions","volume":"110","author":"S Yamada","year":"2004","journal-title":"Circulation"},{"issue":"03","key":"ref170","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1161\/STROKEAHA.107.497305","article-title":"Genetics of intracranial aneurysms","volume":"39","author":"Y M Ruigrok","year":"2008","journal-title":"Stroke"},{"issue":"03","key":"ref171","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s12265-012-9349-8","article-title":"Elastin in large artery stiffness and hypertension","volume":"5","author":"J E Wagenseil","year":"2012","journal-title":"J Cardiovasc Transl Res"},{"issue":"22","key":"ref172","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1093\/hmg\/ddl412","article-title":"Evidence in favor of the contribution of genes involved in the maintenance of the extracellular matrix of the arterial wall to the development of intracranial aneurysms","volume":"15","author":"Y M Ruigrok","year":"2006","journal-title":"Hum Mol Genet"},{"issue":"09","key":"ref173","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1161\/01.STR.0000236499.55301.09","article-title":"The versican gene and the risk of intracranial aneurysms","volume":"37","author":"Y M Ruigrok","year":"2006","journal-title":"Stroke"},{"issue":"02","key":"ref174","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000223438","article-title":"Association analysis of genes involved in the maintenance of the integrity of the extracellular matrix with intracranial aneurysms in a Japanese cohort","volume":"28","author":"Y M Ruigrok","year":"2009","journal-title":"Cerebrovasc Dis"},{"issue":"02","key":"ref175","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nrg1521","article-title":"Genome-wide association studies for common diseases and complex traits","volume":"6","author":"J N Hirschhorn","year":"2005","journal-title":"Nat Rev Genet"},{"issue":"12","key":"ref176","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1038\/ng.240","article-title":"Susceptibility loci for intracranial aneurysm in European and Japanese populations","volume":"40","author":"K Bilguvar","year":"2008","journal-title":"Nat Genet"},{"issue":"05","key":"ref177","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/ng.563","article-title":"Genome-wide association study of intracranial aneurysm identifies three new risk loci","volume":"42","author":"K Yasuno","year":"2010","journal-title":"Nat Genet"},{"issue":"5830","key":"ref178","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1126\/science.1142447","article-title":"A common allele on chromosome 9 associated with coronary heart disease","volume":"316","author":"R McPherson","year":"2007","journal-title":"Science"},{"issue":"05","key":"ref179","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1056\/NEJMoa072366","article-title":"Genomewide association analysis of coronary artery disease","volume":"357","author":"N J Samani","year":"2007","journal-title":"N Engl J Med"},{"issue":"5830","key":"ref180","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1126\/science.1142842","article-title":"A common variant on chromosome 9p21 affects the risk of myocardial infarction","volume":"316","author":"A Helgadottir","year":"2007","journal-title":"Science"},{"issue":"05","key":"ref181","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.jacc.2007.11.087","article-title":"Association of genetic variation on chromosome 9p21 with susceptibility and progression of atherosclerosis: a population-based, prospective study","volume":"52","author":"S Ye","year":"2008","journal-title":"J Am Coll Cardiol"},{"issue":"01","key":"ref182","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/BF03401664","article-title":"The CDKN2A (p16) gene and human cancer","volume":"3","author":"W D Foulkes","year":"1997","journal-title":"Mol Med"},{"issue":"06","key":"ref183","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/ng.361","article-title":"Genome-wide association study identifies eight loci associated with blood pressure","volume":"41","author":"C Newton-Cheh","year":"2009","journal-title":"Nat Genet"},{"issue":"23","key":"ref184","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1212\/WNL.0b013e318295d751","article-title":"Genetic risk factors for intracranial aneurysms: a meta-analysis in more than 116,000 individuals","volume":"80","author":"V S Alg","year":"2013","journal-title":"Neurology"},{"issue":"49","key":"ref185","doi-asserted-by":"crossref","first-page":"19707","DOI":"10.1073\/pnas.1117137108","article-title":"Common variant near the endothelin receptor type A (EDNRA) gene is associated with intracranial aneurysm risk","volume":"108","author":"K Yasuno","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"03","key":"ref186","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1161\/STROKEAHA.114.007286","article-title":"Genetic study of intracranial aneurysms","volume":"46","author":"J Yan","year":"2015","journal-title":"Stroke"},{"issue":"03","key":"ref187","doi-asserted-by":"crossref","first-page":"e0121104","DOI":"10.1371\/journal.pone.0121104","article-title":"Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm","volume":"10","author":"J L Farlow","year":"2015","journal-title":"PLoS One"},{"issue":"05","key":"ref188","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.ajhg.2016.09.001","article-title":"RNF213 is associated with intracranial aneurysms in the French-Canadian population","volume":"99","author":"S Zhou","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"12","key":"ref189","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1161\/STROKEAHA.116.014161","article-title":"THSD1 (thrombospondin type 1 domain containing protein 1) mutation in the pathogenesis of intracranial aneurysm and subarachnoid hemorrhage","volume":"47","author":"T Santiago-Sim","year":"2016","journal-title":"Stroke"},{"issue":"07","key":"ref190","doi-asserted-by":"crossref","first-page":"e002099","DOI":"10.1161\/CIRCGEN.117.002099","article-title":"Rho guanine nucleotide exchange factor ARHGEF17 is a risk gene for intracranial aneurysms","volume":"11","author":"X Yang","year":"2018","journal-title":"Circ Genom Precis Med"},{"issue":"18","key":"ref191","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1097\/WNR.0000000000000289","article-title":"Increased vascular MMP-9 in mice lacking RNF213: moyamoya disease susceptibility gene","volume":"25","author":"S Sonobe","year":"2014","journal-title":"Neuroreport"},{"issue":"07","key":"ref192","doi-asserted-by":"crossref","first-page":"e22542","DOI":"10.1371\/journal.pone.0022542","article-title":"Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development","volume":"6","author":"W Liu","year":"2011","journal-title":"PLoS One"},{"key":"ref193","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.brainres.2014.01.011","article-title":"Temporal profile of the vascular anatomy evaluated by 9.4-T magnetic resonance angiography and histopathological analysis in mice lacking RNF213: a susceptibility gene for moyamoya disease","volume":"1552","author":"S Sonobe","year":"2014","journal-title":"Brain Res"},{"issue":"07","key":"ref194","doi-asserted-by":"crossref","first-page":"e41876","DOI":"10.1371\/journal.pone.0041876","article-title":"Identification of a novel actin-binding domain within the Rho guanine nucleotide exchange factor TEM4","volume":"7","author":"N Mitin","year":"2012","journal-title":"PLoS One"},{"key":"ref195","first-page":"3271","article-title":"TEM4 is a junctional Rho GEF required for cell-cell adhesion, monolayer integrity and barrier function","volume":"126","author":"S P Ngok","year":"2013","journal-title":"J Cell Sci"}],"container-title":["Journal of Neurological Surgery Part A: Central European Neurosurgery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1994-8560.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T02:02:45Z","timestamp":1771380165000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1994-8560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":195,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2026,2,12]]},"published-print":{"date-parts":[[2026,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1994-8560","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2193-6315","2193-6323"],"issn-type":[{"value":"2193-6315","type":"print"},{"value":"2193-6323","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,12,8]]},"published":{"date-parts":[[2022,12,8]]}}}