Perturbations of the cerebrovascular matrisome: A convergent mechanism in small vessel disease of the brain?

Journal of Cerebral Blood Flow and Metabolism

Volumn 36, Issue 1, 2016, Pages 143-157

  Joutel, Anne ^a,b   Haddad, Iman ^c   Ratelade, Julien ^a,b   Nelson, Mark T ^d,e  

^a INSERM   (France)

^b DHU NeuroVasc Paris Sorbonne   (France)

^c PSL RESEARCH UNIVERSITY   (France)

^d UNIVERSITY OF VERMONT   (United States)

^e UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Basement membrane; cerebral small vessel disease; collagen type IV; extracellular matrix; proteomics

Indexed keywords

CEREBROVASCULAR MATRISOME PROTEIN; COLLAGEN TYPE 4; GELATINASE B; GLYCOPROTEIN; HTRA1 PROTEIN; LAMININ; MATRIX METALLOPROTEINASE 19; MITOCHONDRIAL PROTEIN; NOTCH3 RECEPTOR; PROTEIN; PROTEOGLYCAN; PROTEOHEPARAN SULFATE; PROTEOME; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TRANSCRIPTION FACTOR FOXC1; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; SCLEROPROTEIN;

ASTROCYTE; BASEMENT MEMBRANE; BRAIN BLOOD FLOW; BRAIN BLOOD VESSEL; BRAIN CIRCULUS ARTERIOSUS; BRAIN MICROCIRCULATION; BRAIN TISSUE; CADASIL; CARASIL; CEREBROVASCULAR DISEASE; CLINICAL FEATURE; DISEASE ASSOCIATION; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; FAMILIAL DISEASE; GENE MUTATION; HISTOPATHOLOGY; HUMAN; MICROVASCULATURE; NEUROPATHOLOGY; NONHUMAN; PERICYTE; PHYSIOLOGICAL PROCESS; PIA MATER; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEOMICS; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; BRAIN; GENETICS; METABOLISM; MUTATION; PATHOLOGY; VASCULARIZATION;

ANIMALS; BRAIN; CEREBRAL SMALL VESSEL DISEASES; EXTRACELLULAR MATRIX; EXTRACELLULAR MATRIX PROTEINS; HUMANS; MICROVESSELS; MUTATION;

EID: 84951570642     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2015.62     Document Type: Review

References (110)

1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9: 689-701
2. Joutel A. Pathogenic aspects of hereditray small vessel disease of the brain. In: Pantoni L and Gorelick PB (eds) Cerebral Small Vessel Disease. Cambridge University Press, 2014, pp.64-81
3. French CR, Seshadri S, Destefano AL, Fornage M, Arnold CR, Gage PJ, et al. Mutation of FOXC1 and PITX2 induces cerebral small-vessel disease. J Clin Invest 2014; 124: 4877-4881
4. Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110: 673-687
5. Hynes RO. The extracellular matrix: not just pretty fibrils. Science 2009; 326: 1216-1219
6. Naba A, Clauser KR, Hoersch S, Liu H, Carr SA and Hynes RO. The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics 2012; 11: M111.014647
7. Jung J, Ryu T, Hwang Y, Lee E and Lee D. Prediction of extracellular matrix proteins based on distinctive sequence and domain characteristics. J Comput Biol 2010; 17: 97-105
8. Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol 2011; 3: a004978
9. Sarrazin S, Lamanna WC and Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol 2011; 3: pii:a004952
10. Hallmann R, Horn N, Selg M, Wendler O, Pausch F and Sorokin LM. Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 2005; 85: 979-1000
11. Ramirez F and Dietz HC. Fibrillin-rich microfibrils: Structural determinants of morphogenetic and homeostatic events. J Cell Physiol 2007; 213: 326-330
12. Preissner KT and Reuning U. Vitronectin in vascular context: facets of a multitalented matricellular protein. Semin Thromb Hemost 2011; 37: 408-424
13. Schwarzbauer JE and DeSimone DW. Fibronectins, their fibrillogenesis, and in vivo functions. Cold Spring Harb Perspect Biol 2011; 3: pii:a005041
14. Hynes RO and Naba A. Overview of the matrisome-an inventory of extracellular matrix constituents and functions. Cold Spring Harb Perspect Biol 2012; 4: a004903
15. Potente M, Gerhardt H and Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011; 146: 873-887
16. Bonnans C, Chou J and Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014; 15: 786-801
17. Naba A, Hoersch S and Hynes RO. Towards definition of an ECM parts list: an advance on GO categories. Matrix Biol 2012; 31: 371-372
18. The Matrisome Project http://matrisomeproject.mit.edu/
19. Cipolla MJ. The cerebral circulation. In: Granger DN and Granger J (eds) Integrated Systems Physiology: From Molecule to Function. San Rafael, CA: Morgan & Claypool Life Sciences, 2010, pp.1-59
20. Frederickson RG and Low FN. Blood vessels and tissue space associated with the brain of the rat. Am J Anat 1969; 125: 123-145
21. Peters A, Palay SL and de Webster HF. The meninges. The Fine Structure of the Nervous System: Neurons and Their Supporting Cells. Oxford University Press, 1991, pp.395-406
22. Krisch B, Leonhardt H and Oksche A. Compartments and perivascular arrangement of the meninges covering the cerebral cortex of the rat. Cell Tissue Res 1984; 238: 459-474
23. Zhang ET, Inman CB and Weller RO. Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum. J Anat 1990; 170: 111-123
24. Mathiisen TM, Lehre KP, Danbolt NC and Ottersen OP. The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction. Glia 2010; 58: 1094-1103
25. Badhwar A, Stanimirovic DB, Hamel E and Haqqani AS. The proteome of mouse cerebral arteries. J Cereb Blood Flow Metab 2014; 34: 1033-1046
26. Chun HB, Scott M, Niessen S, Hoover H, Baird A, Yates J, et al. The proteome of mouse brain microvessel membranes and basal lamina. J Cereb Blood Flow Metab 2011; 31: 2267-2281
27. Chan FL, Inoue S and Leblond CP. The basement membranes of cryofixed or aldehyde-fixed, freeze-substituted tissues are composed of a lamina densa and do not contain a lamina lucida. Cell Tissue Res 1993; 273: 41-52
28. Yurchenco PD. Basement membranes: cell scaffoldings and signaling platforms. Cold Spring Harb Perspect Biol 2011; 3: pii:a004911
29. Hohenester E and Yurchenco PD. Laminins in basement membrane assembly. Cell Adh Migr 2013; 7: 56-63
30. Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O and Sorokin LM. Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol 2001; 153: 933-946
31. Yousif LF, Di Russo J and Sorokin L. Laminin isoforms in endothelial and perivascular basement membranes. Cell Adh Migr 2013; 7: 101-110
32. Wu C, Ivars F, Anderson P, Hallmann R, Vestweber D, Nilsson P, et al. Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med 2009; 15: 519-527
33. Urabe N, Naito I, Saito K, Yonezawa T, Sado Y, Yoshioka H, et al. Basement membrane type IV collagen molecules in the choroid plexus, pia mater and capillaries in the mouse brain. Arch Histol Cytol 2002; 65: 133-143
34. Khoshnoodi J, Pedchenko V and Hudson BG. Mammalian collagen IV. Microsc Res Tech 2008; 71: 357-370
35. Ho MSP, Böse K, Mokkapati S, Nischt R and Smyth N. Nidogens-Extracellular matrix linker molecules. Microsc Res Tech 2008; 71: 387-395
36. Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, et al. Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol 1999; 144: 151-160
37. Miner JH, Li C, Mudd JL, Go G and Sutherland AE. Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development 2004; 131: 2247-2256
38. Behrens DT, Villone D, Koch M, Brunner G, Sorokin L, Robenek H, et al. The epidermal basement membrane is a composite of separate laminin-or collagen IV-containing networks connected by aggregated perlecan, but not by nidogens. J Biol Chem 2012; 287: 18700-18709
39. Kuo DS, Labelle-Dumais C and Gould DB. COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. Hum Mol Genet 2012; 21: R97-R110
40. Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H, et al. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann Neurol 2013; 73: 48-57
41. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med 2007; 357: 2687-2695
42. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med 2006; 354: 1489-1496
43. Jeanne M, Jorgensen J and Gould DB. Molecular and genetic analysis of collagen type IV mutant mouse models of spontaneous intracerebral hemorrhage identify mechanisms for stroke prevention. Circulation 2015; 131: 1555-1565
44. Kuo DS, Labelle-Dumais C, Mao M, Jeanne M, Kauffman WB, Allen J, et al. Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by Col4a1 and Col4a2 mutations. Hum Mol Genet 2014; 23: 1709-1722
45. Murray LS, Lu Y, Taggart A, Van Regemorter N, Vilain C, Abramowicz M, et al. Chemical chaperone treatment reduces intracellular accumulation of mutant collagen IV and ameliorates the cellular phenotype of a COL4A2 mutation that causes haemorrhagic stroke. Hum Mol Genet 2014; 23: 283-292
46. Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 2005; 308: 1167-1171
47. Lemmens R, Maugeri A, Niessen HWM, Goris A, Tousseyn T, Demaerel P, et al. Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency. Hum Mol Genet 2013; 22: 391-397
48. Pöschl E, Schlötzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y and Mayer U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 2004; 131: 1619-1628
49. Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, et al. Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol 1999; 147: 1109-1122
50. Bader BL, Smyth N, Nedbal S, Miosge N, Baranowsky A, Mokkapati S, et al. Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Mol Cell Biol 2005; 25: 6846-6856
51. Chen Z-L, Yao Y, Norris EH, Kruyer A, Jno-Charles O, Akhmerov A, et al. Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke. J Cell Biol 2013; 202: 381-395
52. Yao Y, Chen Z-L, Norris EH and Strickland S. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun 2014; 5: 3413
53. Miyagoe Y, Hanaoka K, Nonaka I, Hayasaka M, Nabeshima Y, Arahata K, et al. Laminin alpha2 chainnull mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy. FEBS Lett 1997; 415: 33-39
54. Menezes MJ, McClenahan FK, Leiton CV, Aranmolate A, Shan X and Colognato H. The extracellular matrix protein laminin a2 regulates the maturation and function of the blood-brain barrier. J Neurosci 2014; 34: 15260-15280
55. Leitinger B and Hohenester E. Mammalian collagen receptors. Matrix Biol 2007; 26: 146-155
56. Parkin JD, San Antonio JD, Pedchenko V, Hudson B, Jensen ST and Savige J. Mapping structural landmarks, ligand binding sites, and missense mutations to the collagen IV heterotrimers predicts major functional domains, novel interactions, and variation in phenotypes in inherited diseases affecting basement membranes. Hum Mutat 2011; 32: 127-143
57. Turlo KA, Scapa J, Bagher P, Jones AW, Feil R, Korthuis RJ, et al. b1-integrin is essential for vasoregulation and smooth muscle survival in vivo. Arterioscler Thromb Vasc Biol 2013; 33: 2325-2335
58. Yamamoto H, Ehling M, Kato K, Kanai K, van Lessen M, Frye M, et al. Integrin b1 controls VE-cadherin localization and blood vessel stability. Nat Commun 2015; 6: 6429
59. Gould DB, Marchant JK, Savinova OV, Smith RS and John SWM. Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis. Hum Mol Genet 2007; 16: 798-807
60. Tabas I and Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 2011; 13: 184-190
61. Chaudhari N, Talwar P, Parimisetty A, Lefebvre d'Hellencourt C and Ravanan P. A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress. Front Cell Neurosci 2014; 8: 213
62. Hara K, Shiga A, Fukutake T, Nozaki H, Miyashita A, Yokoseki A, et al. Association of HTRA1 mutations and familial ischemic cerebral small-vessel disease. N Engl J Med 2009; 360: 1729-1739
63. Oide T, Nakayama H, Yanagawa S, Ito N, Ikeda S-I and Arima K. Extensive loss of arterial medial smooth muscle cells and mural extracellular matrix in cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Neuropathology 2008; 28: 132-142
64. Nozaki H, Nishizawa M and Onodera O. Features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 2014; 45: 3447-3453
65. An E, Sen S, Park SK, Gordish-Dressman H and Hathout Y. Identification of novel substrates for the serine protease HTRA1 in the human RPE secretome. Invest Ophthalmol Vis Sci 2010; 51: 3379-3386
66. Oka C, Tsujimoto R, Kajikawa M, Koshiba-Takeuchi K, Ina J, Yano M, et al. HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins. Dev 2004; 131: 1041-1053
67. Shiga A, Nozaki H, Yokoseki A, Nihonmatsu M, Kawata H, Kato T, et al. Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-beta1 via cleavage of proTGF-beta1. Hum Mol Genet 2011; 20: 1800-1810
68. Graham JR, Chamberland A, Lin Q, Li XJ, Dai D, Zeng W, et al. Serine protease HTRA1 antagonizes transforming growth factor-b signaling by cleaving its receptors and loss of HTRA1 in vivo enhances bone formation. PLoS ONE 2013; 8: e74094
69. Ge G and Greenspan DS. BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein. J Cell Biol 2006; 175: 111-120
70. Beaufort N, Scharrer E, Kremmer E, Lux V, Ehrmann M, Huber R, et al. Cerebral small vessel disease-related protease HtrA1 processes latent TGF-b binding protein 1 and facilitates TGF-b signaling. Proc Natl Acad Sci USA 2014; 111: 16496-16501
71. Jakobsson L and van Meeteren LA. Transforming growth factor b family members in regulation of vascular function: in the light of vascular conditional knockouts. Exp Cell Res 2013; 319: 1264-1270
72. Gillis E, Van Laer L and Loeys BL. Genetics of thoracic aortic aneurysm: at the crossroad of transforming growth factor-b signaling and vascular smooth muscle cell contractility. Circ Res 2013; 113: 327-340
73. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E and BousserMG. Cadasil. Lancet Neurol 2009; 8: 643-653
74. Fouillade C, Monet-Lepretre M, Baron-Menguy C and Joutel A. Notch signalling in smooth muscle cells during development and disease. Cardiovasc Res 2012; 95: 138-146
75. Joutel A, Vahedi K, Corpechot C, Troesch A, Chabriat H, Vayssiere C, et al. Strong clustering and stereotyped nature of Notch3 mutations in CADASIL patients. Lancet 1997; 350: 1511-1515
76. Dichgans M, Ludwig H, Muller-Hocker J, Messerschmidt A and Gasser T. Small in-frame deletions and missense mutations in CADASIL: 3D models predict misfolding of Notch3 EGF-like repeat domains. Eur J Hum Genet 2000; 8: 280-285
77. Monet-Lepretre M, Haddad I, Baron-Menguy C, Fouillot-Panchal M, Riani M, Domenga-Denier V, et al. Abnormal recruitment of extracellular matrix proteins by excess Notch3 ECD: a new pathomechanism in CADASIL. Brain 2013; 136: 1830-1845
78. Joutel A. Pathogenesis of CADASIL: transgenic and knock-out mice to probe function and dysfunction of the mutated gene, Notch3, in the cerebrovasculature. Bioessays 2011; 33: 73-80
79. Arboleda-Velasquez JF, Manent J, Lee JH, Tikka S, Ospina C, Vanderburg CR, et al. Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral smallvessel disease. Proc Natl Acad Sci USA 2011; 108: E128-E135
80. Kast J, Hanecker P, Beaufort N, Giese A, Joutel A, Dichgans M, et al. Sequestration of latent TGF-b binding protein 1 into CADASIL-related Notch3-ECD deposits. Acta Neuropathol Commun 2014; 2: 96
81. Tikka S, Baumann M, Siitonen M, Pasanen P, Pöyhönen M, Myllykangas L, et al. CADASIL and CARASIL. Brain Pathol 2014; 24: 525-544
82. Joutel A, Monet-Lepretre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Invest 2010; 120: 433-445
83. Cognat E, Cleophax S, Domenga-Denier V and Joutel A. Early white matter changes in CADASIL: evidence of segmental intramyelinic oedema in a pre-clinical mouse model. Acta Neuropathol Commun 2014; 2: 49
84. Dabertrand F, Krøigaard C, Bonev AD, Cognat E, Dalsgaard T, Domenga-Denier V, et al. Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease. Proc Natl Acad Sci USA 2015; 112: E796-E805
85. Brew K and Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta 2010; 1803: 55-71
86. Khokha R, Murthy A and Weiss A. Metalloproteinases and their natural inhibitors in inflammation and immunity. Nat Rev Immunol 2013; 13: 649-665
87. Nagase H, Visse R and Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 2006; 69: 562-573
88. Koide M, Penar PL, Tranmer BI and Wellman GC. Heparin-binding EGF-like growth factor mediates oxyhemoglobin-induced suppression of voltage-dependent potassium channels in rabbit cerebral artery myocytes. Am J Physiol Heart Circ Physiol 2007; 293: H1750-H1759
89. Baker AH, Zaltsman AB, George SJ and Newby AC. Divergent effects of tissue inhibitor of metalloproteinase-1,-2, or-3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis. J Clin Invest 1998; 101: 1478-1487
90. Nishimura DY, Searby CC, Alward WL, Walton D, Craig JE, Mackey DA, et al. A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye. Am J Hum Genet 2001; 68: 364-372
91. Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, et al. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet 2009; 41: 1037-1042
92. Kume T, Deng KY, Winfrey V, Gould DB, Walter MA and Hogan BL. The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus. Cell 1998; 93: 985-996
93. Winnier GE, Kume T, Deng K, Rogers R, Bundy J, Raines C, et al. Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles. Dev Biol 1999; 213: 418-431
94. Siegenthaler JA, Choe Y, Patterson KP, Hsieh I, Li D, Jaminet S-C, et al. Foxc1 is required by pericytes during fetal brain angiogenesis. Biol Open 2013; 2: 647-659
95. Seo S, Singh HP, Lacal PM, Sasman A, Fatima A, Liu T, et al. Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth. Proc Natl Acad Sci USA 2012; 109: 2015-2020
96. Ferrara N. Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action. Mol Biol Cell 2010; 21: 687-690
97. Skarie JM and Link BA. FoxC1 is essential for vascular basement membrane integrity and hyaloid vessel morphogenesis. Invest Ophthalmol Vis Sci 2009; 50: 5026-5034
98. Ogata J, Yamanishi H and Ishibashi-Ueda H. Pathology of cerebral small vessel disease. In: Pantoni L and Gorelick PB (eds) Cerebral Small Vessel Disease. Cambridge University Press, 2014, pp.4-15
99. Farkas E, de Vos RAI, Donka G, Jansen Steur EN, Mihály A and Luiten PGM. Age-related microvascular degeneration in the human cerebral periventricular white matter. Acta Neuropathol (Berl) 2006; 111: 150-157
100. function: in the light of vascular conditional knockouts. Exp Cell Res 2013; 319: 1264-1270
101. Zhang WW and Olsson Y. The angiopathy of subcortical arteriosclerotic encephalopathy (Binswanger's disease): immunohistochemical studies using markers for components of extracellular matrix, smooth muscle actin and endothelial cells. Acta Neuropathol (Berl) 1997; 93: 219-224
102. Hajdu MA, Heistad DD, Siems JE and Baumbach GL. Effects of aging on mechanics and composition of cerebral arterioles in rats. Circ Res 1990; 66: 1747-1754
103. Intengan HD and Schiffrin EL. Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 2000; 36: 312-318
104. Pires PW, Dams Ramos CM, Matin N and Dorrance AM. The effects of hypertension on the cerebral circulation. Am J Physiol Heart Circ Physiol 2013; 304: H1598-H1614
105. Martinez-Lemus LA, Zhao G, Galin- Anes EL and Boone M. Inward remodeling of resistance arteries requires reactive oxygen species-dependent activation of matrix metalloproteinases. Am J Physiol Heart Circ Physiol 2011; 300: H2005-H2015
106. LemariéCA, Tharaux P-L and Lehoux S. Extracellular matrix alterations in hypertensive vascular remodeling. J Mol Cell Cardiol 2010; 48: 433-439
107. Izzard AS, Graham D, Burnham MP, Heerkens EH, Dominiczak AF and Heagerty AM. Myogenic and structural properties of cerebral arteries from the stroke-prone spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 2003; 285: H1489-H1494
108. Baumbach GL, Walmsley JG and Hart MN. Composition and mechanics of cerebral arterioles in hypertensive rats. Am J Pathol 1988; 133: 464-471
109. Iadecola C and Davisson RL. Hypertension and cerebrovascular dysfunction. Cell Metab 2008; 7: 476-484
110. Nishimura N, Schaffer CB, Friedman B, Lyden PD and Kleinfeld D. Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci USA 2007; 104: 365-370.