Skip to main content Accessibility help
×
×
Home

Elastic fibres in health and disease

  • Andrew K. Baldwin (a1), Andreja Simpson (a1), Ruth Steer (a1), Stuart A. Cain (a1) and Cay M. Kielty (a1)...
Abstract

Elastic fibres are insoluble components of the extracellular matrix of dynamic connective tissues such as skin, arteries, lungs and ligaments. They are laid down during development, and comprise a cross-linked elastin core within a template of fibrillin-based microfibrils. Their function is to endow tissues with the property of elastic recoil, and they also regulate the bioavailability of transforming growth factor β. Severe heritable elastic fibre diseases are caused by mutations in elastic fibre components; for example, mutations in elastin cause supravalvular aortic stenosis and autosomal dominant cutis laxa, mutations in fibrillin-1 cause Marfan syndrome and Weill–Marchesani syndrome, and mutations in fibulins-4 and -5 cause autosomal recessive cutis laxa. Acquired elastic fibre defects include dermal elastosis, whereas inflammatory damage to fibres contributes to pathologies such as pulmonary emphysema and vascular disease. This review outlines the latest understanding of the composition and assembly of elastic fibres, and describes elastic fibre diseases and current therapeutic approaches.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Elastic fibres in health and disease
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Elastic fibres in health and disease
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Elastic fibres in health and disease
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Cay M. Kielty, Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of ManchesterM13 9PT, UK. E-mail: cay.kielty@manchester.ac.uk
References
Hide All
1Kielty, C.M. (2006) Elastic fibres in health and disease. Expert Reviews in Molecular Medicine 8, 1-23
2Nistala, H. et al. (2010) Fibrillin-1 and -2 differentially modulate endogenous TGFβ and BMP bioavailability during bone formation. Journal of Cell Biology 190, 1107-1121
3Özbek, S. et al. (2010) The evolution of extracellular matrix. Molecular Biology of the Cell 21, 4300-4305
4Piha-Gossack, A., Sossin, W. and Reinhardt, D.P. (2012) The evolution of extracellular fibrillins and their functional domains. PLoS ONE 7, e33560
5Faury, G. (2001) Function-structure relationship of elastic arteries in evolution: from microfibrils to elastin and elastic fibres. Pathologie Biologie (Paris) 49, 310-325
6Robinson, P.N. et al. (2006) The molecular genetics of Marfan syndrome and related disorders. Journal of Medical Genetics 43, 769-787
7Sugitani, H. et al. (2012) Alternative splicing and tissue-specific elastin misassembly act as biological modifiers of human elastin gene frameshift mutations associated with dominant CL. Journal of Biological Chemistry 287, 22055-22067
8Berk, D.R. et al. (2012) CL: a review. Journal of the American Academy of Dermatology 66, 842.e1-17
9Dagoneau, N. et al. (2004) ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. American Journal of Human Genetics 75, 801-806
10Dyksterhuis, L.B. and Weiss, A.S. (2010) Homology models for domains 21-23 of human tropoelastin shed light on lysine crosslinking. Biochemical and Biophysical Research Communications 396, 870-873
11Baldock, C. et al. (2011) Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. Proceedings of the National Academy of Sciences USA 108, 4322-4327
12Bax, D.V. et al. (2009) Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3. Journal of Biological Chemistry 284, 28616-28623
13Dyksterhuis, L.B. et al. (2007) Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain. Matrix Biology 26, 125-135
14Yeo, G.C. et al. (2012) Tropoelastin bridge region positions the cell-interactive C terminus and contributes to elastic fiber assembly. Proceedings of the National Academy of Sciences USA 109, 2878-2883
15Hubmacher, D., Tiedemann, K. and Reinhardt, D.P. (2006) Fibrillins: from biogenesis of microfibrils to signaling functions. Current Topics in Developmental Biology 75, 93-123
16Ramirez, F. and Sakai, L.Y. (2010) Biogenesis and function of fibrillin assemblies. Cell and Tissue Research 339, 71-82
17Charbonneau, N.L. et al. (2003) Fibrillins can co-assemble in fibrils, but fibrillin fibril composition displays cell-specific differences. Journal of Biological Chemistry 278, 2740-2749
18Zhang, H. et al. (1994) Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices. Journal of Cell Biology 124, 855-863
19Corson, G.M. et al. (2004) Differential expression of fibrillin-3 adds to microfibril variety in human and avian, but not rodent, connective tissues. Genomics 83, 461-472
20Sabatier, L. et al. (2011) Fibrillin-3 expression in human development. Matrix Biology 30, 43-52
21Charbonneau, N.L. et al. (2010) Microfibril structure masks fibrillin-2 in postnatal tissues. Journal of Biological Chemistry 285, 20242-20251
22Brinckmann, J. et al. (2010) Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: potential alteration of cell attachment and storage of TGF-beta. Laboratory Investigation 90, 739-752
23Carta, L. et al. (2006) Fibrillins 1 and 2 perform partially overlapping functions during aortic development. Journal of Biological Chemistry 281, 8016-8023
24Craft, C.S. et al. (2010) Microfibril-associated glycoprotein-1, an extracellular matrix regulator of bone remodeling. Journal of Biological Chemistry 285, 23858-23867
25Jensen, S.A. et al. (2001) Protein interaction studies of MAGP-1 with tropoelastin and fibrillin-1. Journal of Biological Chemistry 276, 39661-39666
26Zilberberg, L. et al. (2012) Specificity of latent TGF-ß binding protein (LTBP) incorporation into matrix: role of fibrillins and FN. Journal of Cellular Physiology 227, 3828-3836
27Lemaire, R. et al. (2007) Microfibril-associated MAGP-2 stimulates elastic fiber assembly. Journal of Biological Chemistry 282, 800-808
28Massam-Wu, T. et al. (2010) Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta. Journal of Cell Science 123, 3006-3018
29Koli, K. et al. (2005) Sequential deposition of latent TGF-beta binding proteins (LTBPs) during formation of the extracellular matrix in human lung fibroblasts. Experimental Cell Research 310, 370-382
30Gibson, M.A. et al. (1995) Bovine latent transforming growth factor beta 1-binding protein 2: molecular cloning, identification of tissue isoforms, and immunolocalization to elastin-associated microfibrils. Molecular Cell Biology 15, 6932-6942
31Baccarani-Contri, M. et al. (1990) Immunocytochemical localization of proteoglycans within normal elastin fibers. European Journal of Cell Biology 53, 305-312
32Trask, B.C. et al. (2000) The microfibrillar proteins MAGP-1 and fibrillin-1 form a ternary complex with the chondroitin sulfate proteoglycan decorin. Biology of the Cell 11, 1499-1507
33Reinboth, B. et al. (2002) Molecular interactions of biglycan and decorin with elastic fiber components: biglycan forms a ternary complex with tropoelastin and microfibril-associated glycoprotein 1. Journal of Biological Chemistry 277, 3950-3957
34Isogai, Z. et al. (2002) Versican interacts with fibrillin-1 and links extracellular microfibrils to other connective tissue networks. Journal of Biological Chemistry 277, 4565-4572
35Tiedemann, K. et al. (2005) Microfibrils at basement membrane zones interact with perlecan via fibrillin-1. Journal of Biological Chemistry 280, 11404-11412
36Hirano, E. et al. (2002) Expression of 36-kDa microfibril-associated glycoprotein (MAGP-36) in human keratinocytes and its localization in skin. Journal of Dermatological Science 28, 60-67
37Gibson, M.A., Kumaratilake, J.S. and Cleary, E.G. (1997) Immunohistochemical and ultrastructural localization of MP78/70 (betaig-h3) in extracellular matrix of developing and mature bovine tissues. Journal of Histochemistry Cytochemistry 45, 1683-1696
38Hayashi, K. et al. (2004) Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: changes in the expression of LOXL during development and growth of mouse tissues. Journal of Molecular Histology 35, 845-55
39Yanagisawa, H. and Davis, E.C. (2010) Unraveling the mechanism of elastic fiber assembly: the roles of short fibulins. International Journal of Biochemical and Cell Biology 42, 1084-1093
40McLaughlin, P.J. et al. (2007) Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. Human Molecular Genetics 16, 3059-3070
41Kobayashi, N. et al. (2007) A comparative analysis of the fibulin protein family. Biochemical characterization, binding interactions, and tissue localization. Journal of Biological Chemistry 282, 11805-11816
42Choudhury, R. et al. (2009) Differential regulation of elastic fiber formation by fibulin-4 and -5. Journal of Biological Chemistry 284, 24553-24567
43McLaughlin, P.J. et al. (2006) Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. Molecular and Cell Biology 26, 1700-1709
44Horiguchi, M. et al. (2009) Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase. Proceedings of the National Academy of Sciences USA 106, 19029-19034
45Yanagisawa, H. et al. (2002) Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 415, 168-171
46Nakamura, T. et al. (2002) Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415, 171-175
47Hirai, M. et al. (2007) Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. Journal of Cell Biology 176, 1061-1071
48Lomas, A.C. et al. (2007) Fibulin-5 binds human smooth-muscle cells through alpha5beta1 and alpha4beta1 integrins, but does not support receptor activation. Biochemical Journal 405, 417-428
49Sengle, G. et al. (2012) Microenvironmental regulation by fibrillin-1. PLoS Genetics 8, e1002425
50Gabriel, L.A. et al. (2012) ADAMTSL4, a secreted glycoprotein widely distributed in the eye, binds fibrillin-1 microfibrils and accelerates microfibril biogenesis. Investigative Ophthalmology and Vision Sciences 53, 461-469
51Bader, H.L. et al. (2012) A disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5) is a novel fibrillin-1-, fibrillin-2-, and heparin-binding member of the ADAMTS superfamily containing a netrin-like module. Matrix Biology 31, 398-411
52Tsutsui, K. et al. (2010) ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation. Journal of Biological Chemistry 285, 4870-4882
53Privitera, S. et al. (1998) The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin/laminin-binding protein. Journal of Biological Chemistry 273, 6319-6326
54Todorovic, V. et al. (2005) Latent TGF-beta binding proteins. International Journal of Biochemistry and Cell Biology 37, 38-41
55Gleizes, P.E. et al. (1996) Identification and characterization of an eight-cysteine repeat of the latent transforming growth factor-beta binding protein-1 that mediates bonding to the latent transforming growth factor-beta1. Journal of Biological Chemistry 271, 29891-29896
56Saharinen, J., Taipale, J. and Keski-Oja, J. (1996) Association of the small latent transforming growth factor-beta with an eight cysteine repeat of its binding protein LTBP-1. EMBO Journal 15, 245-253
57Isogai, Z. et al. (2003) Latent transforming growth factor beta-binding protein 1 interacts with fibrillin and is a microfibril-associated protein. Journal of Biological Chemistry 278, 2750-2757
58Apte, S.S. (2009) A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. Journal of Biological Chemistry 284, 31493-31497
59Gibson, M.A., Kumaratilake, J.S. and Cleary, E.G. (1989) The protein components of the 12-nanometer microfibrils of elastic and nonelastic tissues. Journal of Biological Chemistry 264, 4590-4598
60Cain, S.A. et al. (2006) Proteomic analysis of fibrillin-rich microfibrils. Proteomics 6, 111-122
61Weinbaum, J.S. et al. (2008) Deficiency in microfibril-associated glycoprotein-1 leads to complex phenotypes in multiple organ systems. Journal of Biological Chemistry 283, 25533-25543
62Gibson, M.A. et al. (1998) Microfibril-associated glycoprotein-2 (MAGP-2) is specifically associated with fibrillin-containing microfibrils but exhibits more restricted patterns of tissue localization and developmental expression than its structural relative MAGP-1. Journal of Histochemistry and Cytochemistry 46, 871-886
63Penner, A.S. et al. (2002) Microfibril-associated glycoprotein-2 interacts with fibrillin-1 and fibrillin-2 suggesting a role for MAGP-2 in elastic fiber assembly. Journal of Biological Chemistry 277, 35044-35049
64Hanssen, E. et al. (2004) MAGP-2 has multiple binding regions on fibrillins and has covalent periodic association with fibrillin-containing microfibrils. Journal of Biological Chemistry 279, 29185-29194
65Molnar, J. et al. (2003) Structural and functional diversity of lysyl oxidase and the LOX-like proteins. Biochimica Biophysica Acta 1647, 220-224
66Marson, A. et al. (2005) Homotypic fibrillin-1 interactions in microfibril assembly. Journal of Biological Chemistry 280, 5013-5021
67Cain, S.A. et al. (2008) HS regulates fibrillin-1 N- and C-terminal interactions. Journal of Biological Chemistry 283, 27017-27027
68Hubmacher, D. et al. (2008) Biogenesis of extracellular microfibrils: multimerization of the fibrillin-1 C terminus into bead-like structures enables self-assembly. Proceedings of the National Academy of Sciences USA 105, 6548-6553
69Wagenseil, J.E. and Mecham, R.P. (2007) New insights into elastic fiber assembly. Birth Defects Research C Embryo Today 81, 229-240
70Kinsey, R. et al. (2008) Fibrillin-1 microfibril deposition is dependent on FN assembly. Journal of Cell Science 121, 2696-2704
71Bax, D.V. et al. (2007) Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation. Journal of Cell Science 120, 1383-1392
72Jovanovic, J. et al. (2007) AlphaVbeta6 is a novel receptor for human fibrillin-1. Comparative studies of molecular determinants underlying integrin-rgd affinity and specificity. Journal of Biological Chemistry 282, 6743-6751
73Reinhardt, D.P. et al. (1996) Fibrillin-1: organization in microfibrils and structural properties. Journal of Molecular Biology 258, 104-116
74Baldock, C. et al. (2001) The supramolecular organization of fibrillin-rich microfibrils. Journal of Cell Biology 152, 1045-1056
75Wang, M.C., Lu, Y. and Baldock, C. (2009) Fibrillin microfibrils: a key role for the interbead region in elasticity. Journal of Molecular Biology 388, 168-179
76Qian, R.Q. and Glanville, R.W. (1997) Alignment of fibrillin molecules in elastic microfibrils is defined by transglutaminase-derived cross-links. Biochemistry 36, 15841-15817
77Baldock, C. et al. (2006) Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility. Proceedings of the National Academy of Sciences USA 103, 11922-11927
78Jensen, S.A., Robertson, I.B. and Handford, P.A. (2012) Dissecting the fibrillin microfibril: structural insights into organization and function. Structure 20, 215-225
79Sabatier, L. et al. (2009) Fibrillin assembly requires fibronectin. Molecular Biology of the Cell 20, 846-858
80Tucker, R.P. and Chiquet-Ehrismann, R. (2009) Evidence for the evolution of tenascin and FN early in the chordate lineage. International Journal of Biochemistry and Cell Biology 41, 424-434
81Hubmacher, D. et al. (2011) Homocysteine modifies structural and functional properties of FN and interferes with the FN-fibrillin-1 interaction. Biochemistry 50, 5322-5332
82Reber-Müller, S. et al. (1995) An extracellular matrix protein of jellyfish homologous to mammalian fibrillins forms different fibrils depending on the life stage of the animal. Developmental Biology 169, 662-672
83Dallas, S.L. et al. (2005) FN regulates latent transforming growth factor-beta (TGF beta) by controlling matrix assembly of latent TGF beta-binding protein-1. Journal of Biological Chemistry 280, 18871-18880
84Tiedemann, K. et al. (2001) Interactions of fibrillin-1 with heparin/heparan sulfate, implications for microfibrillar assembly. Journal of Biological Chemistry 276, 36035-36042
85Ritty, T.M. et al. (2003) Fibrillin-1 and -2 contain heparin-binding sites important for matrix deposition and that support cell attachment. Biochemical Journal 375, 425-432
86Cain, S.A. et al. (2005) Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. Journal of Biological Chemistry 280, 30526-30537
87Akhtar, K. et al. (2011) Oxidative modifications of the C-terminal domain of tropoelastin prevent cell binding. Journal of Biological Chemistry 286, 13574-13582
88Gheduzzi, D. et al. (2005) Heparan sulphate interacts with tropoelastin, with some tropoelastin peptides and is present in human dermis elastic fibers. Matrix Biology 24, 15-25
89Ono, R.N. et al. (2009) Latent transforming growth factor beta-binding proteins and fibulins compete for fibrillin-1 and exhibit exquisite specificities in binding sites. Journal of Biological Chemistry 284, 16872-16881
90Kantola, A.K. et al. (2008) Fibronectin and heparin binding domains of latent TGF-beta binding protein (LTBP)-4 mediate matrix targeting and cell adhesion. Experimental Cell Research 314, 2488-2500
91Vehvilainen, P. et al. (2009) Matrix association of latent TGF-beta binding protein-2 (LTBP-2) is dependent on fibrillin-1. Journal of Cellular Physiology 221, 586-593
92Hirani, R. et al. (2007) LTBP-2 specifically interacts with the amino-terminal region of fibrillin-1 and competes with LTBP-1 for binding to this microfibrillar protein. Matrix Biology 26, 213-223
93Hubmacher, D. and Apte, S.S. (2011) Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function. Cellular and Molecular Life Science 68, 3137-3148
94Saito, M. et al. (2011) ADAMTSL6β protein rescues fibrillin-1 microfibril disorder in a Marfan syndrome mouse model through the promotion of fibrillin-1 assembly. Journal of Biological Chemistry 286, 38602-38613
95Kutz, W.E. et al. (2011) ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in extracellular matrix of cultured fibroblasts. Journal of Biological Chemistry 286, 17156-17167
96Rock, M.J. et al. (2004) Molecular basis of elastic fibre formation. Critical interactions and a tropoelastin-fibrillin-1 cross-link. Journal of Biological Chemistry 279, 23748-23758
97Segade, F. et al. (2007) The intracellular form of human MAGP1 elicits a complex and specific transcriptional response. International Journal of Biochemistry and Cell Biology 39, 2303-2313
98Werneck, C.C. et al. (2008) Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury. Blood 111, 4137-4144
99Yeo, G.C., Keeley, F.W. and Weiss, A.S. (2011) Coacervation of tropoelastin. Advances in Colloid Interface Science 167, 94-103
100Cirulis, J.T. and Keeley, F.W. (2010) Kinetics and morphology of self-assembly of an elastin-like polypeptide based on the alternating domain arrangement of human tropoelastin. Biochemistry 49, 5726-5733
101Choi, J. et al. (2009) Analysis of dermal elastic fibres in the absence of fibulin-5 reveals potential roles for fibulin-5 in elastic fibre assembly. Matrix Biology 28, 211-220
102Czirok, A. et al. (2006) Elastic fiber macro-assembly is a hierarchical, cell motion-mediated process. Journal of Cellular Physiology 207, 97-106
103Sato, F. et al. (2007) Distinct steps of cross-linking, self-association, and maturation of tropoelastin are necessary for elastic fiber formation. Journal of Molecular Biology 369, 841-851
104Broekelmann, T.J. et al. (2005) Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain. Journal of Biologcal Chemistry 280, 40939-40947
105El-Hallous, E. et al. (2007) Fibrillin-1 interactions with fibulins depend on the first hybrid domain and provide an adaptor function to tropoelastin. Journal of Biological Chemistry 282, 8935-8946
106Zheng, Q. et al. (2007) Molecular analysis of fibulin-5 function during de novo synthesis of elastic fibres. Molecular and Cellular Biology 27, 1083-1095
107Michaelides, M. et al. (2006) Maculopathy due to the R345W substitution in fibulin-3: distinct clinical features, disease variability, and extent of retinal dysfunction. Investigative Ophthalmology and Vision Sciences 47, 3085-3097
108Marmorstein, L.Y. et al. (2010) Formation and progression of sub-retinal pigment epithelium deposits in Efemp1 mutation knock-in mice: a model for the early pathogenic course of macular degeneration. Human Molecular Genetics 16, 2423-2432
109Dietz, H.C. (2001, updated 2011) Marfan síndrome. Gene Reviews (ed. Pagon, R.A. et al. ) NCBI Bookshelf ID NBK1335 (PMID:20301510) Seattle WA.
110Habashi, J.P. et al. (2006) Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 312, 117-121
111Holm, T.M. et al. (2011) Noncanonical TGFβ signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science 332, 358-361
112Cain, S.A. et al. (2012) Fibrillin-1 mutations causing Weill-Marchesani syndrome and acromicric and geleophysic dysplasias disrupt heparan sulfate interactions. PLoS ONE, 7, e48634
113Jordan, C.D. et al. (2010) Fibrillins in adult human ovary and polycystic ovary syndrome: is fibrillin-3 affected in PCOS? Journal of Histochemistry and Cytochemistry 58, 903-915
114Doyle, J.J., Gerber, E.E. and Dietz, H.C. (2012) Matrix-dependent perturbation of TGFβ signaling and disease. FEBS Letters 586, 2003-2015
115Faivre, L. et al. (2003) In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome. Journal of Medical Genetics 40, 34-36
116Loeys, B.L. et al. (2010) Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome. Science Translational Medicine 2, 23ra20
117Brooke, B.S. et al. (2008) Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. New England Journal of Medicine. 358, 2878-2795
118Detaint, D. et al. (2010) Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome. Archives of Cardiovascular Diseases 103, 317-325
119Möberg, K. et al. (2010) The Ghent Marfan trial – a randomised, double-blind placebo controlled trial with losartan in Marfan patients treated with β-blockers. International Jounrla of Cardiology 157, 354-358
120Xiong, W. et al. (2008) Doxycycline delays aneurysm rupture in a mouse model of Marfan syndrome. Journal of Vascular Surgery 47, 166-172
121Guo, G. et al. (2012) Antagonism of GxxPG fragments ameliorates manifestations of aortic disease in Marfan syndrome mice. Human Molecular Genetics 22, 433-443
122Wagenseil, J.E. and Mecham, R.P. (2012) Elastin in large artery stiffness and hypertension. Journal of Cardiovascular Translational Research 5, 264-273
123Hu, Q. et al. (2006) Inflammatory destruction of elastic fibres in acquired CL is associated with missense alleles in the elastin and fibulin-5 genes. Journal of Investigative Dermatology 126, 283-290
124Urban, Z. et al. (2001) Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene. Human Genetics 109, 512-520
125Micale, L. et al. (2010) Identification and characterization of seven novel mutations of elastin gene in a cohort of patients affected by supravalvular aortic stenosis. European Journal of Human Genetics 18, 317-323
126Urban, Z. et al. (2002) Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome. American Journal of Human Genetics 71, 30-44
127Ge, X. et al. (2012) Modeling supravalvular aortic stenosis syndrome with human induced pluripotent stem cells. Circulation 126, 1695-1704
128Shin, H.J. et al. (2011) Modified simple sliding aortoplasty for preserving the sinotubular junction without using foreign material for congenital supravalvar aortic stenosis. European Journal of Cardio-thoracic Surgery 40, 598-602
129Morris, C.A. and Mervis, C.B. (2000) Williams syndrome and related disorders. Annual Reviews in Genomics and Human Genetics 1, 461-484
130Kaler, S.G. (2011) ATP7A-related copper transport diseases-emerging concepts and future trends. Nature Reviews in Neurology 7, 15-29
131Urban, Z. et al. (2000) Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibres in skin and a subclinical dermal phenotype. Pediatric Dermatology 17, 12-20
132Schubert, C. (2009) The genomic basis of the Williams-Beuren syndrome. Cell and Molecular Life Sciences 66, 1178-1197
133Pober, B.R. (2010) Williams-Beuren syndrome. New England Journal of Medicine 362, 239-252
134Chassaing, N. et al. (2005) Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. Journal of Medical Genetics 42, 881-892
135Uitto, J. et al. (2011) Pseudoxanthoma elasticum: progress in diagnostics and research towards treatment: summary of the 2010 PXE International Research Meeting. American Journal of Medical Genetics A 7, 10
136Bergen, A.A. et al. (2000) Mutations in ABCC6 cause pseudoxanthoma elasticum. Nature Genetics 25, 228-231
137Uitto, J., Li, Q., and Jiang, Q. (2010) Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms. Journal of Investigative Dermatology 130, 661-670
138Georgalas, I. et al. (2011) Pseudoxanthoma elasticum, ocular manifestations, complications and treatment. Clinical and Experimental Optometry 94, 169-180
139Hucthagowder, V. et al. (2006) Fibulin-4: a novel gene for an autosomal recessive CL syndrome. American Journal of Human Genetics 78, 1075-1080
140Renard, M. et al. (2010) Altered TGFβ signalling and cardiovascular manifestations in patients with autosomal recessive CL type I caused by fibulin-4 deficiency. European Journal of Human Genetics 18, 895-901
141Loeys, B. et al. (2002) Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of CL. Human Molecular Genetics 11, 2113-2118
142Claus, S. et al. (2008) A p.C217R mutation in fibulin-5 from CL patients is associated with incomplete extracellular matrix formation in a skin equivalent model. Journal of Investigative Dermatology 128, 1442-1450
143Hucthagowder, V. et al. (2009) Loss-of-function mutations in ATP6V0A2 impair vesicular trafficking, tropoelastin secretion and cell survival. Human Molecular Genetics 18, 2149-2165
144Shifren, A. and Mecham, R.P. (2006) The stumbling block in lung repair of emphysema: elastic fiber assembly. Proceedings of the American Thoracic Society 3, 428-433
145Skidmore, D.L. et al. (2011) Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Δ1-pyrroline-5-carboxylate synthase (P5CS). American Journal of Medical Genetics A. 155A, 1848-1856
146Schena, D. et al. (2008) Buschke-Ollendorff syndrome. International Journal of Dermatology 47, 1159-1161
147Haji-Seyed-Javadi, R. et al. (2012) LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix. Human Mutation 33, 1182-1187
148Morales, J. et al. (2009) Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. American Journal of Human Genetics 85, 558-568
149Le Goff, C. et al. (2008) ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nature Genetics 40, 1119-1123
150Mellody, K. et al. (2006) Marfan syndrome-causing mutations in fibrillin-1 result in gross morphological alterations and highlight the structural importance of the second hybrid domain. Journal of Biological Chemistry 281, 31854-31862
151Charbonneau, N.L. et al. (2010) In vivo studies of mutant fibrillin-1 microfibrils. Journal of Biological Chemistry 285, 24943-24955
152Kirschner, R. et al. (2011) Classical and neonatal Marfan syndrome mutations in fibrillin-1 cause differential protease susceptibilities and protein function. Journal of Biological Chemistry 286, 32810-32823
153Ashworth, J.L. et al. (1999) Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling. Biochemical Journal 340, 171-181
154Judge, D.P. et al. (2004) Evidence for a critical contribution of haploinsufficiency in the complex pathogenesis of Marfan syndrome. Journal of Clinical Investigation 114, 172-181
155Chung, A.W. et al. (2007) Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome. Circulation Research 101, 512-522
156Booms, P. et al. (2006) A fibrillin-1-fragment containing the elastin-binding-protein GxxPG consensus sequence upregulates matrix metalloproteinase-1: biochemical and computational analysis. Journal of Molecular and Cellular Cardiology 40, 234-246
157Jaffe, M. et al. (2012) Transforming growth factor-beta signaling in myogenic cells regulates vascular morphogenesis, differentiation, and matrix synthesis. Arteriosclerosis, Thrombosis and Vascular Biology 32, e1-11
158Neptune, E. et al. (2003) Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nature Genetics 33, 407-411
159Carta, L. et al. (2009) p38 MAPK is an early determinant of promiscuous Smad2/3 signaling in the aortas of fibrillin-1 (Fbn1)-null mice. Journal of Biological Chemistry 284, 5630-5636
160Le Goff, C. et al. (2011) Mutations in the TGFbeta binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. American Journal of Human Genetics 89, 7-14
161Loeys, B.L. et al. (2006) Aneurysm syndromes caused by mutations in the TGF-beta receptor. New England Journal of Medicine 355, 788-798
162Pannu, H. et al. (2005) Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 112, 513-520
163Ades, L.C. et al. (2006) FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. American Journal of Medical Genetics A 140, 1047-1058
164Coucke, P.J. et al. (2006) Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome. Nature Genetics 38, 452-457
165Doyle, A.J. et al. (2012) Mutations in the TGF-β repressor SKI cause Shprintzen-Goldberg syndrome with aortic aneurysm. Nature Genetics 44, 1249-1254
166Geirsson, A. et al. (2012) Modulation of transforming growth factor-β signaling and extracellular matrix production in myxomatous mitral valves by angiotensin II receptor blockers. Circulation 126, S189-197
167Pober, B.R., Johnson, M., and Urban, Z. (2008) Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. Journal of Clinical Investigation 118, 1606-1615
168Kappanayil, M. et al. (2012) Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis. Orphanet Journal of Rare Diseases 7, 61.
169Reversade, B. et al. (2009) Mutations in PYCR1 cause CL with progeroid features. Nature Genetics 41, 1016-1021
170Leao-Teles, E. et al. (2009) De Barsy syndrome and ATP6V0A2-CDG. European Journal of Human Genetics 18, 526
171Urban, Z. et al. (2009) Mutations in LTBP4 cause a syndrome of impaired pulmonary, gastrointestinal, genitourinary, musculoskeletal, and dermal development. American Journal of Human Genetics 85, 593-605
172Basel-Vanagaite, L. et al. (2009) RIN2 deficiency results in macrocephaly, alopecia, CL, and scoliosis: MACS syndrome. American Journal of Human Genetics 85, 254-263
173Segade, F. (2010) Glucose transporter 10 and arterial tortuosity syndrome: the vitamin C connection. FEBS Letters 584, 2990-2994
174Callewaert, B. et al. (2011) New insights into the pathogenesis of autosomal – dominant CL with report of five ELN mutations. Human Mutation 32, 445-455
175Hu, Q. et al. (2006) Inflammatory destruction of elastic fibers in acquired cutis laxa is associated with missense alleles in the elastin and fibulin-5 genes. Journal of Investigative Dermatology 126, 283-290
176Timmer, D.E.M.L. et al. (2009) Acquired CL in childhood Sweet's syndrome. Pediatric Dermatology 26, 358-360
177Karrer, S. et al. (2012) Photodynamic therapy for skin rejuvenation: review and summary of the literature – results of a consensus conference of an expert group for aesthetic photodynamic therapy. JDDG (Journal of the German Society of Dermatology) 11, 137-148
178Lewis, K.G. et al. (2004) Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes. Journal of the American Academy of Dermatology 51, 1-21
179Alves, R. et al. (2010) Pseudoxanthoma elasticum papillary dermal elastolysis: a case report. Dermatology Research Practice pii, 352724
180Pasquali-Ronchetti, I. and Baccarani-Contri, M. (1997) Elastic fiber during development and aging. Microscopy Research Technique 38, 428-435
181Klein, R.J. et al. (2005) Complement factor H polymorphism in age-related macular degeneration. Science 308, 385-389
182Lotery, A.J. (2006) Reduced Secretion of fibulin 5 in age-related macular degeneration and cutis laxa. Human Mutation 27, 568-574
183Ambati, J. and Fowler, B.J. (2012) Mechanisms of Age-related Macular Degeneration. Neuron 75, 26-39
184Atzori, L. et al. (2011) D-penicillamine elastosis perforans serpiginosa: description of two cases and review of the literature. Dermatology Online Journal 17, 3
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Expert Reviews in Molecular Medicine
  • ISSN: -
  • EISSN: 1462-3994
  • URL: /core/journals/expert-reviews-in-molecular-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed