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

A review

View More View Less
  • 1 Departments of Vascular Surgery and
  • 2 Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

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.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

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.

  • 1

    Alnaes MS, , Isaksen J, , Mardal KA, , Romner B, , Morgan MK, & Ingebrigtsen T: Computation of hemodynamics in the circle of Willis. Stroke 38:25002505, 2007

    • Search Google Scholar
    • Export Citation
  • 2

    Arnal JF, , Dinh-Xuan AT, , Pueyo M, , Darblade B, & Rami J: Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci 55:10781087, 1999

    • Search Google Scholar
    • Export Citation
  • 3

    Atlas SW: Magnetic resonance imaging of intracranial aneurysms. Neuroimaging Clin N Am 7:709720, 1997

  • 4

    Azuma N, , Duzgun SA, , Ikeda M, , Kito H, , Akasaka N, & Sasajima T, : Endothelial cell response to different mechanical forces. J Vasc Surg 32:789794, 2000

    • Search Google Scholar
    • Export Citation
  • 5

    Ballermann BJ, , Dardik A, , Eng E, & Liu A: Shear stress and the endothelium. Kidney Int Suppl 67:S100S108, 1998

  • 6

    Balligand JL, , Feron O, & Dessy C: eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues. Physiol Rev 89:481534, 2009

    • Search Google Scholar
    • Export Citation
  • 7

    Bauer R, , Sheehan S, & Meyer 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 4:119131, 1961

    • Search Google Scholar
    • Export Citation
  • 8

    Bergh N, , Ulfhammer E, , Karlsson L, & Jern S: Effects of two complex hemodynamic stimulation profiles on hemostatic genes in a vessel-like environment. Endothelium 15:231238, 2008

    • Search Google Scholar
    • Export Citation
  • 9

    Berk BC: Atheroprotective signaling mechanisms activated by steady laminar flow in endothelial cells. Circulation 117:10821089, 2008

  • 10

    Bilguvar K, , Yasuno K, , Niemelä M, , Ruigrok YM, , von Und Zu Fraunberg M, & van Duijn CM, : Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet 40:14721477, 2008

    • Search Google Scholar
    • Export Citation
  • 11

    Bonneville F, , Sourour N, & Biondi A: Intracranial aneurysms: an overview. Neuroimaging Clin N Am 16::371382, vii, 2006

  • 12

    Bor AS, , Velthuis BK, , Majoie CB, & Rinkel GJ: Configuration of intracranial arteries and development of aneurysms: a follow-up study. Neurology 70:700705, 2008

    • Search Google Scholar
    • Export Citation
  • 13

    Boussel L, , Rayz V, , McCulloch C, , Martin A, , Acevedo-Bolton G, & Lawton M, : Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study. Stroke 39:29973002, 2008

    • Search Google Scholar
    • Export Citation
  • 14

    Brooks AR, , Lelkes PI, & Rubanyi GM: Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol Genomics 9:2741, 2002

    • Search Google Scholar
    • Export Citation
  • 15

    Canham PB, & Finlay HM: Morphometry of medial gaps of human brain artery branches. Stroke 35:11531157, 2004

  • 16

    Castro MA, , Putman CM, & Cebral JR: Computational fluid dynamics modeling of intracranial aneurysms: effects of parent artery segmentation on intra-aneurysmal hemodynamics. AJNR Am J Neuroradiol 27:17031709, 2006

    • Search Google Scholar
    • Export Citation
  • 17

    Cebral JR, , Castro MA, , Burgess JE, , Pergolizzi RS, , Sheridan MJ, & Putman CM: Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models. AJNR Am J Neuroradiol 26:25502559, 2005

    • Search Google Scholar
    • Export Citation
  • 18

    Cebral JR, , Castro MA, , Soto O, , Löhner R, & Alperin N: Blood-flow models of the circle of Willis from magnetic resonance data. J Eng Math 47:369386, 2003

    • Search Google Scholar
    • Export Citation
  • 19

    Chachisvilis M, , Zhang YL, & Frangos JA: G protein-coupled receptors sense fluid shear stress in endothelial cells. Proc Natl Acad Sci U S A 103:1546315468, 2006

    • Search Google Scholar
    • Export Citation
  • 20

    Chatzizisis YS, , Coskun AU, , Jonas M, , Edelman ER, , Feldman CL, & Stone 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 49:23792393, 2007

    • Search Google Scholar
    • Export Citation
  • 21

    Cheng C, , Helderman F, , Tempel D, , Segers D, , Hierck B, & Poelmann R, : Large variations in absolute wall shear stress levels within one species and between species. Atherosclerosis 195:225235, 2007

    • Search Google Scholar
    • Export Citation
  • 22

    Cheng C, , van Haperen R, , de Waard M, , van Damme LC, , Tempel D, & Hanemaaijer L, : Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique. Blood 106:36913698, 2005

    • Search Google Scholar
    • Export Citation
  • 23

    Chien A, , Tateshima S, , Castro M, , Sayre J, , Cebral J, & Viñuela F: Patient-specific flow analysis of brain aneurysms at a single location: comparison of hemodynamic characteristics in small aneurysms. Med Biol Eng Comput 46:11131120, 2008

    • Search Google Scholar
    • Export Citation
  • 24

    Chow CL, & Ong AC: Autosomal dominant polycystic kidney disease. Clin Med 9:278283, 2009

  • 25

    Dardik A, , Chen L, , Frattini J, , Asada H, , Aziz F, & Kudo FA, : Differential effects of orbital and laminar shear stress on endothelial cells. J Vasc Surg 41:869880, 2005

    • Search Google Scholar
    • Export Citation
  • 26

    Dardik A, , Liu A, & Ballermann BJ: Chronic in vitro shear stress stimulates endothelial cell retention on prosthetic vascular grafts and reduces subsequent in vivo neointimal thickness. J Vasc Surg 29:157167, 1999

    • Search Google Scholar
    • Export Citation
  • 27

    Dardik A, , Yamashita A, , Aziz F, , Asada H, & Sumpio BE: Shear stress-stimulated endothelial cells induce smooth muscle cell chemotaxis via platelet-derived growth factor-BB and interleukin-1alpha. J Vasc Surg 41:321331, 2005

    • Search Google Scholar
    • Export Citation
  • 28

    De Keulenaer GW, , Chappell DC, , Ishizaka N, , Nerem RM, , Alexander RW, & Griendling KK: Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res 82:10941101, 1998

    • Search Google Scholar
    • Export Citation
  • 29

    de Paepe A, , van Landegem W, , de Keyser F, & de Reuck J: Association of multiple intracranial aneurysms and collagen type III deficiency. Clin Neurol Neurosurg 90:5356, 1988

    • Search Google Scholar
    • Export Citation
  • 30

    DeBakey ME, , Lawrie GM, & Glaeser DH: Patterns of atherosclerosis and their surgical significance. Ann Surg 201:115131, 1985

  • 31

    Du W, , Mills I, & Sumpio 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 28:14851491, 1995

    • Search Google Scholar
    • Export Citation
  • 32

    Eftekhar B, , Dadmehr M, , Ansari S, , Ghodsi M, , Nazparvar B, & Ketabchi 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 6:22, 2006

    • Search Google Scholar
    • Export Citation
  • 33

    Eng E, & Ballermann BJ: Diminished NF-kappaB activation and PDGF-B expression in glomerular endothelial cells subjected to chronic shear stress. Microvasc Res 65:137144, 2003

    • Search Google Scholar
    • Export Citation
  • 34

    Finlay HM, , Whittaker P, & Canham PB: Collagen organization in the branching region of human brain arteries. Stroke 29:15951601, 1998

  • 35

    Fisher CM, , Gore I, , Okabe N, & White PD: Calcification of the carotid siphon. Circulation 32:538548, 1965

  • 36

    Fisher M, & Fieman S: Geometric factors of the bifurcation in carotid atherogenesis. Stroke 21:267271, 1990

  • 37

    Foutrakis GN, , Yonas H, & Sclabassi RJ: Finite element methods in the simulation and analysis of intracranial blood flow. Neurol Res 19:174186, 1997

    • Search Google Scholar
    • Export Citation
  • 38

    Foutrakis GN, , Yonas H, & Sclabassi RJ: Saccular aneurysm formation in curved and bifurcating arteries. AJNR Am J Neuroradiol 20:13091317, 1999

    • Search Google Scholar
    • Export Citation
  • 39

    Frangos SG, , Gahtan V, & Sumpio B: Localization of atherosclerosis: role of hemodynamics. Arch Surg 134:11421149, 1999

  • 40

    Frösen J, , Piippo A, , Paetau A, , Kangasniemi M, , Niemelä M, & Hernesniemi J, : Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35:22872293, 2004

    • Search Google Scholar
    • Export Citation
  • 41

    Fukuda S, , Hashimoto N, , Naritomi H, , Nagata I, , Nozaki K, & Kondo S, : Prevention of rat cerebral aneurysm formation by inhibition of nitric oxide synthase. Circulation 101:25322538, 2000

    • Search Google Scholar
    • Export Citation
  • 42

    Gao L, , Hoi Y, , Swartz DD, , Kolega J, , Siddiqui A, & Meng H: Nascent aneurysm formation at the basilar terminus induced by hemodynamics. Stroke 39:20852090, 2008

    • Search Google Scholar
    • Export Citation
  • 43

    Gaucher C, , Devaux C, , Boura C, , Lacolley P, , Stoltz JF, & Menu P: In vitro impact of physiological shear stress on endothelial cells gene expression profile. Clin Hemorheol Microcirc 37:99107, 2007

    • Search Google Scholar
    • Export Citation
  • 44

    Glagov S, , Zarins C, , Giddens DP, & Ku DN: Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 112:10181031, 1988

    • Search Google Scholar
    • Export Citation
  • 45

    Gosling RG, , Newman DL, , Bowden NL, & Twinn KW: The area ration of normal aortic junctions. Aortic configuration and pulse-wave reflection. Br J Radiol 44:850853, 1971

    • Search Google Scholar
    • Export Citation
  • 46

    Grond-Ginsbach C, , Schnippering H, , Hausser I, , Weber R, , Werner I, & Steiner HH, : Ultrastructural connective tissue aberrations in patients with intracranial aneurysms. Stroke 33:21922196, 2002

    • Search Google Scholar
    • Export Citation
  • 47

    Hassan T, , Timofeev EV, , Saito T, , Shimizu H, , Ezura M, & Matsumoto 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 103:662680, 2005

    • Search Google Scholar
    • Export Citation
  • 48

    Hobson RW II, , Wilson SE, & Veith FJ: Vascular Surgery: Principles and Practice ed 3 New York, Marcel Dekker, 2004

  • 49

    Hoi Y, , Meng H, , Woodward SH, , Bendok BR, , Hanel RA, & Guterman LR, : Effects of arterial geometry on aneurysm growth: three-dimensional computational fluid dynamics study. J Neurosurg 101:676681, 2004

    • Search Google Scholar
    • Export Citation
  • 50

    Hoi Y, , Woodward SH, , Kim M, , Taulbee DB, & Meng H: Validation of CFD simulations of cerebral aneurysms with implication of geometric variations. J Biomech Eng 128:844851, 2006

    • Search Google Scholar
    • Export Citation
  • 51

    Hoogstraten HW, , Kootstra JG, , Hillen B, , Krijger JK, & Wensing PJ: Numerical simulation of blood flow in an artery with two successive bends. J Biomech 29:10751083, 1996

    • Search Google Scholar
    • Export Citation
  • 52

    Horikoshi T, , Akiyama I, , Yamagata Z, , Sugita M, & Nukui H: Magnetic resonance angiographic evidence of sex-linked variations in the circle of Willis and the occurrence of cerebral aneurysms. J Neurosurg 96:697703, 2002

    • Search Google Scholar
    • Export Citation
  • 53

    Humphrey JD, & Taylor CA: Intracranial and abdominal aortic aneurysms: similarities, differences, and need for a new class of computational models. Annu Rev Biomed Eng 10:221246, 2008

    • Search Google Scholar
    • Export Citation
  • 54

    Ingebrigtsen T, , Morgan MK, , Faulder K, , Ingebrigtsen L, , Sparr T, & Schirmer H: Bifurcation geometry and the presence of cerebral artery aneurysms. J Neurosurg 101:108113, 2004

    • Search Google Scholar
    • Export Citation
  • 55

    Isaksen JG, , Bazilevs Y, , Kvamsdal T, , Zhang Y, , Kaspersen JH, & Waterloo K, : Determination of wall tension in cerebral artery aneurysms by numerical simulation. Stroke 39:31723178, 2008

    • Search Google Scholar
    • Export Citation
  • 56

    Kaazempur-Mofrad MR, , Isasi AG, , Younis HF, , Chan RC, , Hinton DP, & Sukhova G, : Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology. Ann Biomed Eng 32:932946, 2004

    • Search Google Scholar
    • Export Citation
  • 57

    Kadohama T, , Akasaka N, , Nishimura K, , Hoshino Y, , Sasajima T, & Sumpio BE: p38 Mitogen-activated protein kinase activation in endothelial cell is implicated in cell alignment and elongation induced by fluid shear stress. Endothelium 13:4350, 2006

    • Search Google Scholar
    • Export Citation
  • 58

    Kapoor K, , Singh B, & Dewan LI: Variations in the configuration of the circle of Willis. Anat Sci Int 83:96106, 2008

  • 59

    Karino T, & Goldsmith HL: Particle flow behavior in models of branching vessels. II. Effects of branching angle and diameter ratio on flow patterns. Biorheology 22:87104, 1985

    • Search Google Scholar
    • Export Citation
  • 60

    Kasuya H, , Shimizu T, , Nakaya K, , Sasahara A, , Hori T, & Takakura 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 45:8994, 1999

    • Search Google Scholar
    • Export Citation
  • 61

    Kayembe KN, , Sasahara M, & Hazama F: Cerebral aneurysms and variations in the circle of Willis. Stroke 15:846850, 1984

  • 62

    Kilic T, , Sohrabifar M, , Kurtkaya O, , Yildirim O, , Elmaci I, & Günel M, : Expression of structural proteins and angiogenic factors in normal arterial and unruptured and ruptured aneurysm walls. Neurosurgery 57:9971007, 2005

    • Search Google Scholar
    • Export Citation
  • 63

    Kissela BM, , Sauerbeck L, , Woo D, , Khoury J, , Carrozzella J, & Pancioli A, : Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke 33:13211326, 2002

    • Search Google Scholar
    • Export Citation
  • 64

    Kleinstreuer C: Biofluid Dynamics: Principles and Selected Applications Boca Raton, FL, CRC Press, 2006

  • 65

    Kondo S, , Hashimoto N, , Kikuchi H, , Hazama F, , Nagata I, & Kataoka H: Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke 29:181189, 1998

    • Search Google Scholar
    • Export Citation
  • 66

    Kondo S, , Hashimoto N, , Kikuchi H, , Hazama F, , Nagata I, & Kataoka H: Cerebral aneurysms arising at nonbranching sites. An experimental Study. Stroke 28:398404, 1997

    • Search Google Scholar
    • Export Citation
  • 67

    Korenaga R, , Ando J, , Kosaki K, , Isshiki M, , Takada Y, & Kamiya A: Negative transcriptional regulation of the VCAM-1 gene by fluid shear stress in murine endothelial cells. Am J Physiol 273:C1506C1515, 1997

    • Search Google Scholar
    • Export Citation
  • 68

    Krex D, , König IR, , Ziegler A, , Schackert HK, & Schackert 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 18:104110, 2004

    • Search Google Scholar
    • Export Citation
  • 69

    Ku DN: Blood flow in arteries. Annu Rev Fluid Mech 29:399434, 1997

  • 70

    Ku DN, , Giddens DP, , Zarins CK, & Glagov S: Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:293302, 1985

    • Search Google Scholar
    • Export Citation
  • 71

    Kuivaniemi H, , Prockop DJ, , Wu Y, , Madhatheri SL, , Kleinert C, & Earley 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 43:26522658, 1993

    • Search Google Scholar
    • Export Citation
  • 72

    Lee RM: Morphology of cerebral arteries. Pharmacol Ther 66:149173, 1995

  • 73

    Lee SW, , Antiga L, , Spence JD, & Steinman DA: Geometry of the carotid bifurcation predicts its exposure to disturbed flow. Stroke 39:23412347, 2008

    • Search Google Scholar
    • Export Citation
  • 74

    Li YS, , Haga JH, & Chien S: Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech 38:19491971, 2005

  • 75

    Libby P, , Geng YJ, , Aikawa M, , Schoenbeck U, , Mach F, & Clinton SK, : Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 7:330335, 1996

    • Search Google Scholar
    • Export Citation
  • 76

    Lin MC, , Almus-Jacobs F, , Chen HH, , Parry GC, , Mackman N, & Shyy JY, : Shear stress induction of the tissue factor gene. J Clin Invest 99:737744, 1997

    • Search Google Scholar
    • Export Citation
  • 77

    Lum RM, , Wiley LM, & Barakat AI: Influence of different forms of fluid shear stress on vascular endothelial TGF-beta1 mRNA expression. Int J Mol Med 5:635641, 2000

    • Search Google Scholar
    • Export Citation
  • 78

    Malek A, & Izumo S: Physiological fluid shear stress causes downregulation of endothelin-1 mRNA in bovine aortic endothelium. Am J Physiol 263:C389C396, 1992

    • Search Google Scholar
    • Export Citation
  • 79

    Malek AM, , Jiang L, , Lee I, , Sessa WC, , Izumo S, & Alper 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 254:231242, 1999

    • Search Google Scholar
    • Export Citation
  • 80

    Marshall I, , Zhao S, , Papathanasopoulou P, , Hoskins P, & Xu Y: MRI and CFD studies of pulsatile flow in healthy and stenosed carotid bifurcation models. J Biomech 37:679687, 2004

    • Search Google Scholar
    • Export Citation
  • 81

    Masuda H, , Zhuang YJ, , Singh TM, , Kawamura K, , Murakami M, & Zarins CK, : Adaptive remodeling of internal elastic lamina and endothelial lining during flow-induced arterial enlargement. Arterioscler Thromb Vasc Biol 19:22982307, 1999

    • Search Google Scholar
    • Export Citation
  • 82

    Meng H, , Swartz DD, , Wang Z, , Hoi Y, , Kolega J, & Metaxa EM, : A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo. Neurosurgery 59:10941101, 2006

    • Search Google Scholar
    • Export Citation
  • 83

    Meng H, , Wang Z, , Hoi Y, , Gao L, , Metaxa E, & Swartz DD, : Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke 38:19241931, 2007

    • Search Google Scholar
    • Export Citation
  • 84

    Metaxa E, , Meng H, , Kaluvala SR, , Szymanski MP, , Paluch RA, & Kolega J: Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow. Am J Physiol Heart Circ Physiol 295:H736H742, 2008

    • Search Google Scholar
    • Export Citation
  • 85

    Mohan S, , Hamuro M, , Sorescu GP, , Koyoma K, , Sprague EA, & Jo H, : IκBα-dependent regulation of low-shear flow-induced NF-κB activity: role of nitric oxide. Am J Physiol Cell Physiol 284:C1039C1047, 2003

    • Search Google Scholar
    • Export Citation
  • 86

    Mohan S, , Mohan N, & Sprague EA: Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments. Am J Physiol 273:C572C578, 1997

    • Search Google Scholar
    • Export Citation
  • 87

    Motomiya M, & Karino T: Flow patterns in the human carotid artery bifurcation. Stroke 15:5056, 1984

  • 88

    Nagel T, , Resnick N, , Atkinson WJ, , Dewey CF Jr, & Gimbrone MA Jr: Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J Clin Invest 94:885891, 1994

    • Search Google Scholar
    • Export Citation
  • 89

    Nahed BV, , Bydon M, , Ozturk AK, , Bilguvar K, , Bayrakli F, & Gunel M: Genetics of intracranial aneurysms. Neurosurgery 60:213226, 2007

  • 90

    Nguyen KT, , Clark CD, , Chancellor TJ, & Papavassiliou DV: Carotid geometry effects on blood flow and on risk for vascular disease. J Biomech 41:1119, 2008

    • Search Google Scholar
    • Export Citation
  • 91

    Oluwole BO, , Du W, , Mills I, & Sumpio BE: Gene regulation by mechanical forces. Endothelium 5:8593, 1997

  • 92

    Onda H, , Kasuya H, , Yoneyama T, , Takakura K, , Hori T, & Takeda J, : Genomewide-linkage and haplotype-association studies map intracranial aneurysm to chromosome 7q11. Am J Hum Genet 69:804819, 2001

    • Search Google Scholar
    • Export Citation
  • 93

    Osawa M, , Masuda M, , Kusano K, & Fujiwara 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 158:773785, 2002

    • Search Google Scholar
    • Export Citation
  • 94

    Osborn AG: Diagnostic Cerebral Angiography ed 2 Philadelphia, Lippincott Williams & Wilkins, 1999

  • 95

    Oshima M, , Kobayashi T, & Takagi K: Biosimulation and visualization: effect of cerebrovascular geometry on hemodynamics. Ann N Y Acad Sci 972:337344, 2002

    • Search Google Scholar
    • Export Citation
  • 96

    Oshima M, , Torii R, , Kobayashi T, , Taniguchi N, & Takagi K: Finite element simulation of blood flow in the cerebral artery. Comput Methods Appl Mech Eng 191:661671, 2001

    • Search Google Scholar
    • Export Citation
  • 97

    Oyre S, , Ringgaard S, , Kozerke S, , Paaske WP, , Erlandsen M, & Boesiger 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 32:128134, 1998

    • Search Google Scholar
    • Export Citation
  • 98

    Painter PR, , Edén P, & Bengtsson HU: Pulsatile blood flow, shear force, energy dissipation and Murray's Law. Theor Biol Med Model 3:31, 2006

    • Search Google Scholar
    • Export Citation
  • 99

    Prado CM, , Ramos SG, , Alves-Filho JC, , Elias J Jr, , Cunha FQ, & Rossi MA: Turbulent flow/low wall shear stress and stretch differentially affect aorta remodeling in rats. J Hypertens 24:503515, 2006

    • Search Google Scholar
    • Export Citation
  • 100

    Raghavan ML, , Ma B, & Harbaugh RE: Quantified aneurysm shape and rupture risk. J Neurosurg 102:355362, 2005

  • 101

    Ravensbergen J, , Krijger JK, , Hillen B, & Hoogstraten HW: The influence of the angle of confluence on the flow in a vertebrobasilar junction model. J Biomech 29:281299, 1996

    • Search Google Scholar
    • Export Citation
  • 102

    Ravensbergen J, , Krijger JK, , Verdaasdonk AL, , Hillen B, & Hoogstraten HW: The influence of the blunting of the apex on the flow in a vertebro-basilar junction model. J Biomech Eng 119:195205, 1997

    • Search Google Scholar
    • Export Citation
  • 103

    Ravensbergen J, , Ravensbergen JW, , Krijger JK, , Hillen B, & Hoogstraten HW: Localizing role of hemodynamics in atherosclerosis in several human vertebrobasilar junction geometries. Arterioscler Thromb Vasc Biol 18:708716, 1998

    • Search Google Scholar
    • Export Citation
  • 104

    Rhoton AL Jr: Aneurysms. Neurosurgery 51:4 Suppl S121S158, 2002

  • 105

    Rhoton AL Jr: The cerebrum. Anatomy Neurosurgery 61:1 Suppl 37119, 2007

  • 106

    Riedel M, , Rafflenbeul W, & Lichtlen P: Ovarian sex steroids and atherosclerosis. Clin Investig 71:406412, 1993

  • 107

    Rindt CC, & Steenhoven AA: Unsteady flow in a rigid 3-D model of the carotid artery bifurcation. J Biomech Eng 118:9096, 1996

  • 108

    Rizzoni D, , Porteri E, , Castellano M, , Bettoni G, , Muiesan ML, & Tiberio G, : Endothelial dysfunction in hypertension is independent from the etiology and from vascular structure. Hypertension 31:335341, 1998

    • Search Google Scholar
    • Export Citation
  • 109

    Ruigrok YM, & Rinkel GJ: Genetics of intracranial aneurysms. Stroke 39:10491055, 2008

  • 110

    Sadamasa N, , Nozaki K, & Hashimoto N: Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms. Stroke 34:29802984, 2003

    • Search Google Scholar
    • Export Citation
  • 111

    Samijo SK, , Willigers JM, , Barkhuysen R, , Kitslaar PJ, , Reneman RS, & Brands PJ, : Wall shear stress in the human common carotid artery as function of age and gender. Cardiovasc Res 39:515522, 1998

    • Search Google Scholar
    • Export Citation
  • 112

    Schirmer CM, & Malek AM: Estimation of wall shear stress dynamic fluctuations in intracranial atherosclerotic lesions using computational fluid dynamics. Neurosurgery 63:326335, 2008

    • Search Google Scholar
    • Export Citation
  • 113

    Schirmer CM, & Malek AM: Prediction of complex flow patterns in intracranial atherosclerotic disease using computational fluid dynamics. Neurosurgery 61:842852, 2007

    • Search Google Scholar
    • Export Citation
  • 114

    Schulz UG, & Rothwell PM: Major variation in carotid bifurcation anatomy: a possible risk factor for plaque development?. Stroke 32:25222529, 2001

    • Search Google Scholar
    • Export Citation
  • 115

    Schulz UG, & Rothwell PM: Sex differences in carotid bifurcation anatomy and the distribution of atherosclerotic plaque. Stroke 32:15251531, 2001

    • Search Google Scholar
    • Export Citation
  • 116

    Sharma R, , Yellowley CE, , Civelek M, , Ainslie K, , Hodgson L, & Tarbell JM, : Intracellular calcium changes in rat aortic smooth muscle cells in response to fluid flow. Ann Biomed Eng 30:371378, 2002

    • Search Google Scholar
    • Export Citation
  • 117

    Shojima M, , Oshima M, , Takagi K, , Torii R, , Hayakawa M, & Katada K, : Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamic study of 20 middle cerebral artery aneurysms. Stroke 35:25002505, 2004

    • Search Google Scholar
    • Export Citation
  • 118

    Shojima M, , Oshima M, , Takagi K, , Torii R, , Nagata K, & Shirouzu I, : Role of the bloodstream impacting force and the local pressure elevation in the rupture of cerebral aneurysms. Stroke 36:19331938, 2005

    • Search Google Scholar
    • Export Citation
  • 119

    Silacci P, , Formentin K, , Bouzourène K, , Daniel F, , Brunner HR, & Hayoz D: Unidirectional and oscillatory shear stress differentially modulate NOS III gene expression. Nitric Oxide 4:4756, 2000

    • Search Google Scholar
    • Export Citation
  • 120

    Steinman DA, , Milner JS, , Norley CJ, , Lownie SP, & Holdsworth DW: Image-based computational simulation of flow dynamics in a giant intracranial aneurysm. AJNR Am J Neuroradiol 24:559566, 2003

    • Search Google Scholar
    • Export Citation
  • 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 13:744746, 1991

    • Search Google Scholar
    • Export Citation
  • 122

    Sumpio BE, , Yun S, , Cordova AC, , Haga M, , Zhang J, & Koh 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 280:1118511191, 2005

    • Search Google Scholar
    • Export Citation
  • 123

    Tateshima S, , Murayama Y, , Villablanca JP, , Morino T, , Nomura K, & Tanishita K, : In vitro measurement of fluid-induced wall shear stress in unruptured cerebral aneurysms harboring blebs. Stroke 34:187192, 2003

    • Search Google Scholar
    • Export Citation
  • 124

    Thomas JB, , Antiga L, , Che SL, , Milner JS, , Steinman DA, & Spence JD, : Variation in the carotid bifurcation geometry of young versus older adults: implications for geometric risk of atherosclerosis. Stroke 36:24502456, 2005

    • Search Google Scholar
    • Export Citation
  • 125

    Thomas JB, , Milner JS, & Steinman DA: On the influence of vessel planarity on local hemodynamics at the human carotid bifurcation. Biorheology 39:443448, 2002

    • Search Google Scholar
    • Export Citation
  • 126

    Thubrikar MJ, & Robicsek F: Pressure-induced arterial wall stress and atherosclerosis. Ann Thorac Surg 59:15941603, 1995

  • 127

    Toda M, , Yamamoto K, , Shimizu N, , Obi S, , Kumagaya S, & Igarashi T, : Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. J Biotechnol 133:239244, 2008

    • Search Google Scholar
    • Export Citation
  • 128

    Topper JN, , Cai J, , Falb D, & Gimbrone 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 93:1041710422, 1996

    • Search Google Scholar
    • Export Citation
  • 129

    Torres VE, , Pirson Y, & Wiebers DO: Cerebral aneurysms. N Engl J Med 355:27032705, 2006. (Letter)

  • 130

    van den Beld AW, , Bots ML, , Janssen JA, , Pols HA, , Lamberts SW, & Grobbee DE: Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol 157:2531, 2003

    • Search Google Scholar
    • Export Citation
  • 131

    von Eckardstein A: Risk factors for atherosclerotic vascular disease. Handb Exp Pharmacol 170 71105, 2005

  • 132

    Vouyouka AG, , Powell RJ, , Ricotta J, , Chen H, , Dudrick DJ, & Sawmiller CJ, : Ambient pulsatile pressure modulates endothelial cell proliferation. J Mol Cell Cardiol 30:609615, 1998

    • Search Google Scholar
    • Export Citation
  • 133

    Walford G, & Loscalzo J: Nitric oxide in vascular biology. J Thromb Haemost 1:21122118, 2003

  • 134

    Wang Z, , Kolega J, , Hoi Y, , Gao L, , Swartz DD, & Levy EI, : Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation. Neurosurgery 65:169178, 2009

    • Search Google Scholar
    • Export Citation
  • 135

    Weir B: Unruptured intracranial aneurysms: a review. J Neurosurg 96:342, 2002

  • 136

    Wetzel S, , Meckel S, , Frydrychowicz A, , Bonati L, , Radue EW, & Scheffler K, : In vivo assessment and visualization of intracranial arterial hemodynamics with flow-sensitized 4D MR imaging at 3T. AJNR Am J Neuroradiol 28:433438, 2007

    • Search Google Scholar
    • Export Citation
  • 137

    White CR, & Frangos JA: The shear stress of it all: the cell membrane and mechanochemical transduction. Philos Trans R Soc Lond B Biol Sci 362:14591467, 2007

    • Search Google Scholar
    • Export Citation
  • 138

    Wityk RJ, , Lehman D, , Klag M, , Coresh J, , Ahn H, & Litt B: Race and sex differences in the distribution of cerebral atherosclerosis. Stroke 27:19741980, 1996

    • Search Google Scholar
    • Export Citation
  • 139

    Wong LK: Global burden of intracranial atherosclerosis. Int J Stroke 1:158159, 2006

  • 140

    Yamashita S, , Isoda H, , Hirano M, , Takeda H, , Inagawa S, & Takehara Y, : Visualization of hemodynamics in intracranial arteries using time-resolved three-dimensional phase-contrast MRI. J Magn Reson Imaging 25:473478, 2007

    • Search Google Scholar
    • Export Citation
  • 141

    Younis HF, , Kaazempur-Mofrad MR, , Chan RC, , Isasi AG, , Hinton DP, & Chau AH, : Hemodynamics and wall mechanics in human carotid bifurcation and its consequences for atherogenesis: investigation of inter-individual variation. Biomech Model Mechanobiol 3:1732, 2004

    • Search Google Scholar
    • Export Citation
  • 142

    Zarins CK, , Giddens DP, , Bharadvaj BK, , Sottiurai VS, , Mabon RF, & Glagov S: Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res 53:502514, 1983

    • Search Google Scholar
    • Export Citation
  • 143

    Ziegler T, , Bouzourène K, , Harrison VJ, , Brunner HR, & Hayoz 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 18:686692, 1998

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 994 519 44
Full Text Views 354 72 13
PDF Downloads 179 38 4
EPUB Downloads 0 0 0