The critical role of hemodynamics in the development of cerebral vascular disease

A review

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Atherosclerosis and intracranial saccular aneurysms predictably localize in areas with complex arterial geometries such as bifurcations and curvatures. These sites are characterized by unique hemodynamic conditions that possibly influence the risk for these disorders. One hemodynamic parameter in particular has emerged as a key regulator of vascular biology—wall shear stress (WSS). Variations in geometry can change the distribution and magnitude of WSS, thus influencing the risk for vascular disorders. Computer simulations conducted using patient-specific data have suggested that departures from normal levels of WSS lead to aneurysm formation and progression. In addition, multiple studies indicate that disturbed flow and low WSS predispose patients to extracranial atherosclerosis, and particularly to carotid artery disease. Conversely, in the case of intracranial atherosclerosis, more studies are needed to provide a firm link between hemodynamics and atherogenesis. The recognition of WSS as an important factor in cerebral vascular disease may help to identify individuals at risk and guide treatment options.

Abbreviations used in this paper: BA = basilar artery; CA = carotid artery; CFD = computational fluid dynamics; ECA = external CA; eNOS = endothelial nitric oxide synthase; ICA = internal CA; iNOS = inducible NO synthase; ISA = intracranial saccular aneurysm; MAPK = mitogen-activated protein kinase; MCA = middle cerebral artery; NF-κB = nuclear factor–kappa B; VA = vertebral artery; WSS = wall shear stress.

Article Information

Address correspondence to: Bauer E. Sumpio, M.D., Ph.D., Department of Vascular Surgery, Yale University School of Medicine, 333 Cedar Street, BB 204, New Haven, Connecticut 06520. email: Bauer.sumpio@yale.edu.

Please include this information when citing this paper: published online November 27, 2009; DOI: 10.3171/2009.10.JNS09759.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Left: Distribution of aneurysms in the circle of Willis. Approximately 90% of aneurysms occur in the anterior circulation, and most commonly (30–35%) in the anterior communicating artery (ACoA) complex (see Bonneville et al.). The darker color indicates the presence of saccular aneurysms. Right: Distribution of atherosclerosis in the intracranial vasculature. Dark color denotes areas afflicted by atherosclerosis, which usually involves the CA siphon. ACA = anterior cerebral artery; AICA = anterior inferior cerebellar artery; PCA = posterior cerebral artery; PCoA = posterior communicating artery; PICA = posterior inferior cerebellar artery; SCA = superior cerebellar artery.

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    Computed tomography angiography images demonstrating the origin of intracranial aneurysms (red arrows) at the junction of asymmetrical ACAs (white arrows). Please note that the aneurysm points away from the dominant ACA. Thick-cut maximum intensity projection images (A and C) and 3D reconstructions (B and D) of different ruptured aneurysms are shown.

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    Variations in bifurcation angles may influence the risk of aneurysm initiation and atherosclerosis. An increase in bifurcation angles has been associated with aneurysm formation. As the angles get wider, blood flow from the parent artery is obstructed, and as a result the WSS levels rise around the CA apex. A recent study by Lee et al. has linked variations in the proximal area ratio to disturbed flow patterns in the CA.

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    An idealized aneurysm forming on the outer curve of a curved artery. Due to centrifugal forces, blood enters through the distal aneurysm neck and impacts on the aneurysm wall. The site of impact experiences a local increase of wall stress (normal stress), whereas areas directly adjacent to the impact site experience high levels of WSS. Increases in curvature (1/R), or in the diameter of the neck may increase the levels of WSS. After impact, blood flow may follow the outline of the aneurysm and exit at the proximal neck. It should be noted that not all aneurysms conform to this flow pattern. Blood can enter through the proximal neck, and the site of flow impingement and maximal WSS may vary (for examples of an aneurysm dome see Castro et al., Cebral et al.,17 and Tateshima et al.).

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    The interplay between systemic factors and mechanical factors may lead to aneurysm formation.

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    Disturbed laminar flow includes flow patterns such as separation and recirculation. Endothelial cells sense changes in the hemodynamic environment and change their gene expression profile, possibly in an attempt to normalize WSS levels. Expression of NO is suppressed and release of various proinflammatory and prothrombotic factors ensues. IFN-γ = interferon-γ; IL-1 = interleukin-1; TNF = tumor necrosis factor.

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    The CA bifurcation is a common site for atherosclerotic lesions. The presence of the CA sinus promotes the generation of secondary flow patterns. Early lesions localize at the outer wall of the ICA, which correlates accurately with areas of disturbed flow (see Ku et al. and Zarins et al.). The outer wall of the ECA can also be affected. The apex and the inner walls of the ICA and ECA are exposed to normal or high levels of WSS and are thus spared in the early stages of atherogenesis. If stenosis occurs, then the flow patterns change and the aforementioned areas might be at risk (see Kaazempur-Mofrad et al.).

References

1

Alnaes MSIsaksen JMardal KARomner BMorgan MKIngebrigtsen T: Computation of hemodynamics in the circle of Willis. Stroke 38:250025052007

2

Arnal JFDinh-Xuan ATPueyo MDarblade BRami J: Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci 55:107810871999

3

Atlas SW: Magnetic resonance imaging of intracranial aneurysms. Neuroimaging Clin N Am 7:7097201997

4

Azuma NDuzgun SAIkeda MKito HAkasaka NSasajima T: Endothelial cell response to different mechanical forces. J Vasc Surg 32:7897942000

5

Ballermann BJDardik AEng ELiu A: Shear stress and the endothelium. Kidney Int Suppl 67:S100S1081998

6

Balligand JLFeron ODessy C: eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev 89:4815342009

7

Bauer RSheehan SMeyer JS: Arteriographic study of cerebrovascular disease. II. Cerebral symptoms due to kinking, tortuosity, and compression of carotid and vertebral arteries in the neck. Arch Neurol 4:1191311961

8

Bergh NUlfhammer EKarlsson LJern S: Effects of two complex hemodynamic stimulation profiles on hemostatic genes in a vessel-like environment. Endothelium 15:2312382008

9

Berk BC: Atheroprotective signaling mechanisms activated by steady laminar flow in endothelial cells. Circulation 117:108210892008

10

Bilguvar KYasuno KNiemelä MRuigrok YMvon Und Zu Fraunberg Mvan Duijn CM: Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet 40:147214772008

11

Bonneville FSourour NBiondi A: Intracranial aneurysms: an overview. Neuroimaging Clin N Am 16::371382vii2006

12

Bor ASVelthuis BKMajoie CBRinkel GJ: Configuration of intracranial arteries and development of aneurysms: a follow-up study. Neurology 70:7007052008

13

Boussel LRayz VMcCulloch CMartin AAcevedo-Bolton GLawton M: Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study. Stroke 39:299730022008

14

Brooks ARLelkes PIRubanyi GM: Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol Genomics 9:27412002

15

Canham PBFinlay HM: Morphometry of medial gaps of human brain artery branches. Stroke 35:115311572004

16

Castro MAPutman CMCebral JR: Computational fluid dynamics modeling of intracranial aneurysms: effects of parent artery segmentation on intra-aneurysmal hemodynamics. AJNR Am J Neuroradiol 27:170317092006

17

Cebral JRCastro MABurgess JEPergolizzi RSSheridan MJPutman CM: Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models. AJNR Am J Neuroradiol 26:255025592005

18

Cebral JRCastro MASoto OLöhner RAlperin N: Blood-flow models of the circle of Willis from magnetic resonance data. J Eng Math 47:3693862003

19

Chachisvilis MZhang YLFrangos JA: G protein-coupled receptors sense fluid shear stress in endothelial cells. Proc Natl Acad Sci U S A 103:15463154682006

20

Chatzizisis YSCoskun AUJonas MEdelman ERFeldman CLStone PH: Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J Am Coll Cardiol 49:237923932007

21

Cheng CHelderman FTempel DSegers DHierck BPoelmann R: Large variations in absolute wall shear stress levels within one species and between species. Atherosclerosis 195:2252352007

22

Cheng Cvan Haperen Rde Waard Mvan Damme LCTempel DHanemaaijer L: Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique. Blood 106:369136982005

23

Chien ATateshima SCastro MSayre JCebral JViñuela F: Patient-specific flow analysis of brain aneurysms at a single location: comparison of hemodynamic characteristics in small aneurysms. Med Biol Eng Comput 46:111311202008

24

Chow CLOng AC: Autosomal dominant polycystic kidney disease. Clin Med 9:2782832009

25

Dardik AChen LFrattini JAsada HAziz FKudo FA: Differential effects of orbital and laminar shear stress on endothelial cells. J Vasc Surg 41:8698802005

26

Dardik ALiu ABallermann BJ: Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness. J Vasc Surg 29:1571671999

27

Dardik AYamashita AAziz FAsada HSumpio BE: Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1alpha. J Vasc Surg 41:3213312005

28

De Keulenaer GWChappell DCIshizaka NNerem RMAlexander RWGriendling KK: Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res 82:109411011998

29

de Paepe Avan Landegem Wde Keyser Fde Reuck J: Association of multiple intracranial aneurysms and collagen type III deficiency. Clin Neurol Neurosurg 90:53561988

30

DeBakey MELawrie GMGlaeser DH: Patterns of atherosclerosis and their surgical significance. Ann Surg 201:1151311985

31

Du WMills ISumpio BE: Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE binding protein and NF-kB, in endothelial cells: species and vascular bed diversity. J Biomech 28:148514911995

32

Eftekhar BDadmehr MAnsari SGhodsi MNazparvar BKetabchi E: Are the distributions of variations of circle of Willis different in different populations? Results of an anatomical study and review of literature. BMC Neurol 6:222006

33

Eng EBallermann BJ: Diminished NF-kappaB activation and PDGF-B expression in glomerular endothelial cells subjected to chronic shear stress. Microvasc Res 65:1371442003

34

Finlay HMWhittaker PCanham PB: Collagen organization in the branching region of human brain arteries. Stroke 29:159516011998

35

Fisher CMGore IOkabe NWhite PD: Calcification of the carotid siphon. Circulation 32:5385481965

36

Fisher MFieman S: Geometric factors of the bifurcation in carotid atherogenesis. Stroke 21:2672711990

37

Foutrakis GNYonas HSclabassi RJ: Finite element methods in the simulation and analysis of intracranial blood flow. Neurol Res 19:1741861997

38

Foutrakis GNYonas HSclabassi RJ: Saccular aneurysm formation in curved and bifurcating arteries. AJNR Am J Neuroradiol 20:130913171999

39

Frangos SGGahtan VSumpio B: Localization of atherosclerosis: role of hemodynamics. Arch Surg 134:114211491999

40

Frösen JPiippo APaetau AKangasniemi MNiemelä MHernesniemi J: Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35:228722932004

41

Fukuda SHashimoto NNaritomi HNagata INozaki KKondo S: Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase. Circulation 101:253225382000

42

Gao LHoi YSwartz DDKolega JSiddiqui AMeng H: Nascent aneurysm formation at the basilar terminus induced by hemodynamics. Stroke 39:208520902008

43

Gaucher CDevaux CBoura CLacolley PStoltz JFMenu P: In vitro impact of physiological shear stress on endothelial cells gene expression profile. Clin Hemorheol Microcirc 37:991072007

44

Glagov SZarins CGiddens DPKu DN: Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 112:101810311988

45

Gosling RGNewman DLBowden NLTwinn KW: The area ration of normal aortic junctions. Aortic configuration and pulse-wave reflection. Br J Radiol 44:8508531971

46

Grond-Ginsbach CSchnippering HHausser IWeber RWerner ISteiner HH: Ultrastructural connective tissue aberrations in patients with intracranial aneurysms. Stroke 33:219221962002

47

Hassan TTimofeev EVSaito TShimizu HEzura MMatsumoto Y: A proposed parent vessel geometry-based categorization of saccular intracranial aneurysms: computational flow dynamics analysis of the risk factors for lesion rupture. J Neurosurg 103:6626802005

48

Hobson RW IIWilson SEVeith FJ: Vascular Surgery: Principles and Practice ed 3New YorkMarcel Dekker2004

49

Hoi YMeng HWoodward SHBendok BRHanel RAGuterman LR: Effects of arterial geometry on aneurysm growth: three-dimensional computational fluid dynamics study. J Neurosurg 101:6766812004

50

Hoi YWoodward SHKim MTaulbee DBMeng H: Validation of CFD simulations of cerebral aneurysms with implication of geometric variations. J Biomech Eng 128:8448512006

51

Hoogstraten HWKootstra JGHillen BKrijger JKWensing PJ: Numerical simulation of blood flow in an artery with two successive bends. J Biomech 29:107510831996

52

Horikoshi TAkiyama IYamagata ZSugita MNukui H: Magnetic resonance angiographic evidence of sex-linked variations in the circle of Willis and the occurrence of cerebral aneurysms. J Neurosurg 96:6977032002

53

Humphrey JDTaylor CA: Intracranial and abdominal aortic aneurysms: similarities, differences, and need for a new class of computational models. Annu Rev Biomed Eng 10:2212462008

54

Ingebrigtsen TMorgan MKFaulder KIngebrigtsen LSparr TSchirmer H: Bifurcation geometry and the presence of cerebral artery aneurysms. J Neurosurg 101:1081132004

55

Isaksen JGBazilevs YKvamsdal TZhang YKaspersen JHWaterloo K: Determination of wall tension in cerebral artery aneurysms by numerical simulation. Stroke 39:317231782008

56

Kaazempur-Mofrad MRIsasi AGYounis HFChan RCHinton DPSukhova G: Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology. Ann Biomed Eng 32:9329462004

57

Kadohama TAkasaka NNishimura KHoshino YSasajima TSumpio BE: p38 Mitogen-activated protein kinase activation in endothelial cell is implicated in cell alignment and elongation induced by fluid shear stress. Endothelium 13:43502006

58

Kapoor KSingh BDewan LI: Variations in the configuration of the circle of Willis. Anat Sci Int 83:961062008

59

Karino TGoldsmith HL: Particle flow behavior in models of branching vessels. II. Effects of branching angle and diameter ratio on flow patterns. Biorheology 22:871041985

60

Kasuya HShimizu TNakaya KSasahara AHori TTakakura K: Angeles between A1 and A2 segments of the anterior cerebral artery visualized by three-dimensional computed tomographic angiography and association of anterior communicating artery aneurysms. Neurosurgery 45:89941999

61

Kayembe KNSasahara MHazama F: Cerebral aneurysms and variations in the circle of Willis. Stroke 15:8468501984

62

Kilic TSohrabifar MKurtkaya OYildirim OElmaci IGünel M: Expression of structural proteins and angiogenic factors in normal arterial and unruptured and ruptured aneurysm walls. Neurosurgery 57:99710072005

63

Kissela BMSauerbeck LWoo DKhoury JCarrozzella JPancioli A: Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke 33:132113262002

64

Kleinstreuer C: Biofluid Dynamics: Principles and Selected Applications Boca Raton, FLCRC Press2006

65

Kondo SHashimoto NKikuchi HHazama FNagata IKataoka H: Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke 29:1811891998

66

Kondo SHashimoto NKikuchi HHazama FNagata IKataoka H: Cerebral aneurysms arising at nonbranching sites. An experimental Study. Stroke 28:3984041997

67

Korenaga RAndo JKosaki KIsshiki MTakada YKamiya A: Negative transcriptional regulation of the VCAM-1 gene by fluid shear stress in murine endothelial cells. Am J Physiol 273:C1506C15151997

68

Krex DKönig IRZiegler ASchackert HKSchackert G: Extended single nucleotide polymorphism and haplotype analysis of the elastin gene in Caucasians with intracranial aneurysms provides evidence for racially/ethnically based differences. Cerebrovasc Dis 18:1041102004

69

Ku DN: Blood flow in arteries. Annu Rev Fluid Mech 29:3994341997

70

Ku DNGiddens DPZarins CKGlagov S: Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:2933021985

71

Kuivaniemi HProckop DJWu YMadhatheri SLKleinert CEarley JJ: Exclusion of mutations in the gene for type III collagen (COL3A1) as a common cause of intracranial aneurysms or cervical artery dissections: results from sequence analysis of the coding sequences of type III collagen from 55 unrelated patients. Neurology 43:265226581993

72

Lee RM: Morphology of cerebral arteries. Pharmacol Ther 66:1491731995

73

Lee SWAntiga LSpence JDSteinman DA: Geometry of the carotid bifurcation predicts its exposure to disturbed flow. Stroke 39:234123472008

74

Li YSHaga JHChien S: Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech 38:194919712005

75

Libby PGeng YJAikawa MSchoenbeck UMach FClinton SK: Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 7:3303351996

76

Lin MCAlmus-Jacobs FChen HHParry GCMackman NShyy JY: Shear stress induction of the tissue factor gene. J Clin Invest 99:7377441997

77

Lum RMWiley LMBarakat AI: Influence of different forms of fluid shear stress on vascular endothelial TGF-beta1 mRNA expression. Int J Mol Med 5:6356412000

78

Malek AIzumo S: Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium. Am J Physiol 263:C389C3961992

79

Malek AMJiang LLee ISessa WCIzumo SAlper SL: Induction of nitric oxide synthase mRNA by shear stress requires intracellular calcium and G-protein signals and is modulated by PI 3 kinase. Biochem Biophys Res Commun 254:2312421999

80

Marshall IZhao SPapathanasopoulou PHoskins PXu Y: MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models. J Biomech 37:6796872004

81

Masuda HZhuang YJSingh TMKawamura KMurakami MZarins CK: Adaptive remodeling of internal elastic lamina and endothelial lining during flow-induced arterial enlargement. Arterioscler Thromb Vasc Biol 19:229823071999

82

Meng HSwartz DDWang ZHoi YKolega JMetaxa EM: A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo. Neurosurgery 59:109411012006

83

Meng HWang ZHoi YGao LMetaxa ESwartz DD: Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke 38:192419312007

84

Metaxa EMeng HKaluvala SRSzymanski MPPaluch RAKolega J: Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow. Am J Physiol Heart Circ Physiol 295:H736H7422008

85

Mohan SHamuro MSorescu GPKoyoma KSprague EAJo H: IκBα-dependent regulation of low-shear flow-induced NF-κB activity: role of nitric oxide. Am J Physiol Cell Physiol 284:C1039C10472003

86

Mohan SMohan NSprague EA: Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments. Am J Physiol 273:C572C5781997

87

Motomiya MKarino T: Flow patterns in the human carotid artery bifurcation. Stroke 15:50561984

88

Nagel TResnick NAtkinson WJDewey CF JrGimbrone MA Jr: Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J Clin Invest 94:8858911994

89

Nahed BVBydon MOzturk AKBilguvar KBayrakli FGunel M: Genetics of intracranial aneurysms. Neurosurgery 60:2132262007

90

Nguyen KTClark CDChancellor TJPapavassiliou DV: Carotid geometry effects on blood flow and on risk for vascular disease. J Biomech 41:11192008

91

Oluwole BODu WMills ISumpio BE: Gene regulation by mechanical forces. Endothelium 5:85931997

92

Onda HKasuya HYoneyama TTakakura KHori TTakeda J: Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. Am J Hum Genet 69:8048192001

93

Osawa MMasuda MKusano KFujiwara K: Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: is it a mechanoresponsive molecule?. J Cell Biol 158:7737852002

94

Osborn AG: Diagnostic Cerebral Angiography ed 2PhiladelphiaLippincott Williams & Wilkins1999

95

Oshima MKobayashi TTakagi K: Biosimulation and visualization: effect of cerebrovascular geometry on hemodynamics. Ann N Y Acad Sci 972:3373442002

96

Oshima MTorii RKobayashi TTaniguchi NTakagi K: Finite element simulation of blood flow in the cerebral artery. Comput Methods Appl Mech Eng 191:6616712001

97

Oyre SRinggaard SKozerke SPaaske WPErlandsen MBoesiger P: Accurate noninvasive quantitation of blood flow, cross-sectional lumen vessel area and wall shear stress by three-dimensional paraboloid modeling of magnetic resonance imaging velocity data. J Am Coll Cardiol 32:1281341998

98

Painter PREdén PBengtsson HU: Pulsatile blood flow, shear force, energy dissipation and Murray's Law. Theor Biol Med Model 3:312006

99

Prado CMRamos SGAlves-Filho JCElias J JrCunha FQRossi MA: Turbulent flow/low wall shear stress and stretch differentially affect aorta remodeling in rats. J Hypertens 24:5035152006

100

Raghavan MLMa BHarbaugh RE: Quantified aneurysm shape and rupture risk. J Neurosurg 102:3553622005

101

Ravensbergen JKrijger JKHillen BHoogstraten HW: The influence of the angle of confluence on the flow in a vertebrobasilar junction model. J Biomech 29:2812991996

102

Ravensbergen JKrijger JKVerdaasdonk ALHillen BHoogstraten HW: The influence of the blunting of the apex on the flow in a vertebro-basilar junction model. J Biomech Eng 119:1952051997

103

Ravensbergen JRavensbergen JWKrijger JKHillen BHoogstraten HW: Localizing role of hemodynamics in atherosclerosis in several human vertebrobasilar junction geometries. Arterioscler Thromb Vasc Biol 18:7087161998

104

Rhoton AL Jr: Aneurysms. Neurosurgery 51:4 SupplS121S1582002

105

Rhoton AL Jr: The cerebrum. Anatomy Neurosurgery 61:1 Suppl371192007

106

Riedel MRafflenbeul WLichtlen P: Ovarian sex steroids and atherosclerosis. Clin Investig 71:4064121993

107

Rindt CCSteenhoven AA: Unsteady flow in a rigid 3-D model of the carotid artery bifurcation. J Biomech Eng 118:90961996

108

Rizzoni DPorteri ECastellano MBettoni GMuiesan MLTiberio G: Endothelial dysfunction in hypertension is independent from the etiology and from vascular structure. Hypertension 31:3353411998

109

Ruigrok YMRinkel GJ: Genetics of intracranial aneurysms. Stroke 39:104910552008

110

Sadamasa NNozaki KHashimoto N: Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms. Stroke 34:298029842003

111

Samijo SKWilligers JMBarkhuysen RKitslaar PJReneman RSBrands PJ: Wall shear stress in the human common carotid artery as function of age and gender. Cardiovasc Res 39:5155221998

112

Schirmer CMMalek AM: Estimation of wall shear stress dynamic fluctuations in intracranial atherosclerotic lesions using computational fluid dynamics. Neurosurgery 63:3263352008

113

Schirmer CMMalek AM: Prediction of complex flow patterns in intracranial atherosclerotic disease using computational fluid dynamics. Neurosurgery 61:8428522007

114

Schulz UGRothwell PM: Major variation in carotid bifurcation anatomy: a possible risk factor for plaque development?. Stroke 32:252225292001

115

Schulz UGRothwell PM: Sex differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque. Stroke 32:152515312001

116

Sharma RYellowley CECivelek MAinslie KHodgson LTarbell JM: Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow. Ann Biomed Eng 30:3713782002

117

Shojima MOshima MTakagi KTorii RHayakawa MKatada K: Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamic study of 20 middle cerebral artery aneurysms. Stroke 35:250025052004

118

Shojima MOshima MTakagi KTorii RNagata KShirouzu I: Role of the bloodstream impacting force and the local pressure elevation in the rupture of cerebral aneurysms. Stroke 36:193319382005

119

Silacci PFormentin KBouzourène KDaniel FBrunner HRHayoz D: Unidirectional and oscillatory shear stress differentially modulate NOS III gene expression. Nitric Oxide 4:47562000

120

Steinman DAMilner JSNorley CJLownie SPHoldsworth DW: Image-based computational simulation of flow dynamics in a giant intracranial aneurysm. AJNR Am J Neuroradiol 24:5595662003

121

Sumpio BE: Hemodynamic forces and the biology of the endothelium: signal transduction pathways in endothelial cells subjected to physical forces in vitro. J Vasc Surg 13:7447461991

122

Sumpio BEYun SCordova ACHaga MZhang JKoh Y: MAPKs (ERK1/2, p38) and AKT can be phosphorylated by shear stress independently of platelet endothelial cell adhesion molecule-1 (CD31) in vascular endothelial cells. J Biol Chem 280:11185111912005

123

Tateshima SMurayama YVillablanca JPMorino TNomura KTanishita K: In vitro measurement of fluid-induced wall shear stress in unruptured cerebral aneurysms harboring blebs. Stroke 34:1871922003

124

Thomas JBAntiga LChe SLMilner JSSteinman DASpence JD: Variation in the carotid bifurcation geometry of young versus older adults: implications for geometric risk of atherosclerosis. Stroke 36:245024562005

125

Thomas JBMilner JSSteinman DA: On the influence of vessel planarity on local hemodynamics at the human carotid bifurcation. Biorheology 39:4434482002

126

Thubrikar MJRobicsek F: Pressure-induced arterial wall stress and atherosclerosis. Ann Thorac Surg 59:159416031995

127

Toda MYamamoto KShimizu NObi SKumagaya SIgarashi T: Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. J Biotechnol 133:2392442008

128

Topper JNCai JFalb DGimbrone MA Jr: Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci U S A 93:10417104221996

129

Torres VEPirson YWiebers DO: Cerebral aneurysms. N Engl J Med 355:270327052006. (Letter)

130

van den Beld AWBots MLJanssen JAPols HALamberts SWGrobbee DE: Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol 157:25312003

131

von Eckardstein A: Risk factors for atherosclerotic vascular disease. Handb Exp Pharmacol 170711052005

132

Vouyouka AGPowell RJRicotta JChen HDudrick DJSawmiller CJ: Ambient pulsatile pressure modulates endothelial cell proliferation. J Mol Cell Cardiol 30:6096151998

133

Walford GLoscalzo J: Nitric oxide in vascular biology. J Thromb Haemost 1:211221182003

134

Wang ZKolega JHoi YGao LSwartz DDLevy EI: Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation. Neurosurgery 65:1691782009

135

Weir B: Unruptured intracranial aneurysms: a review. J Neurosurg 96:3422002

136

Wetzel SMeckel SFrydrychowicz ABonati LRadue EWScheffler K: In vivo assessment and visualization of intracranial arterial hemodynamics with flow-sensitized 4D MR imaging at 3T. AJNR Am J Neuroradiol 28:4334382007

137

White CRFrangos JA: The shear stress of it all: the cell membrane and mechanochemical transduction. Philos Trans R Soc Lond B Biol Sci 362:145914672007

138

Wityk RJLehman DKlag MCoresh JAhn HLitt B: Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 27:197419801996

139

Wong LK: Global burden of intracranial atherosclerosis. Int J Stroke 1:1581592006

140

Yamashita SIsoda HHirano MTakeda HInagawa STakehara Y: Visualization of hemodynamics in intracranial arteries using time-resolved three-dimensional phase-contrast MRI. J Magn Reson Imaging 25:4734782007

141

Younis HFKaazempur-Mofrad MRChan RCIsasi AGHinton DPChau AH: Hemodynamics and wall mechanics in human carotid bifurcation and its consequences for atherogenesis: investigation of inter-individual variation. Biomech Model Mechanobiol 3:17322004

142

Zarins CKGiddens DPBharadvaj BKSottiurai VSMabon RFGlagov S: Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res 53:5025141983

143

Ziegler TBouzourène KHarrison VJBrunner HRHayoz D: Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. Arterioscler Thromb Vasc Biol 18:6866921998

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