Elastin biosynthesis: The missing link in tissue-engineered blood vessels

Patel, Aavishkar A.; Fine, Benjamin; Sandig, Martin; Mequanint, Kibret

doi:10.1016/j.cardiores.2006.02.021

Cited by 286 publications

(229 citation statements)

References 96 publications

(74 reference statements)

Supporting

Mentioning

223

Contrasting

Order By: Relevance

“…Our data show that the RGD motif of fibrillin-1 is recognized by at least three different integrin receptors with a large spectrum of binding affinities and provide novel insights into structural requirements and cellular consequences of these interactions. These results may find application in the understanding of the mouse Tsk phenotype, which is caused by secretion of a fibrillin-1 polypeptide with a duplication of RGD-containing TB4 domain, and also in the advancement of vascular tissue grafts, where the current challenge is to develop a cell-adhesive matrix that supports selective cell adhesion and activity without the risk of thrombosis (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

αVβ6 Is a Novel Receptor for Human Fibrillin-1

Jovanović¹,

Takagi²,

Choulier³

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human fibrillin-1, the major structural protein of connective tissue 10 -12 nm microfibrils, contains multiple calcium binding epidermal growth factor-like domains interspersed with transforming growth factor ␤-binding protein-like (TB) domains. TB4 contains a flexible RGD loop that mediates cell adhesion via ␣V␤3 and ␣5␤1 integrins. This study identifies integrin ␣V␤6 as a novel cellular receptor for fibrillin-1 with a K d of ϳ0.45 M. Analyses of this interaction by surface plasmon resonance and immunocytochemistry reveal different module requirements for ␣V␤6 activation compared with those of ␣V␤3, suggesting that a covalent linkage of an N-terminal calcium binding epidermal growth factor-like domain to TB4 can modulate ␣V integrin binding specificity. Furthermore, our data suggest ␣5␤1 is a low affinity fibrillin-1 receptor (K d > 1 M), thus providing a molecular explanation for the different ␣5␤1 distribution patterns seen when human keratinocytes and fibroblasts are plated on recombinant fibrillin fragments versus those derived from the physiological ligand fibronectin. Nonfocal contact distribution of ␣5␤1 suggests that its engagement by fibrillin-1 may elicit a lesser degree and/or different type of intracellular signaling compared with that seen with a high affinity ligand.Human fibrillin-1, a 350-kDa extracellular matrix glycoprotein, is the major structural component of the 10 -12-nm connective tissue microfibrils (1). It has a modular structure dominated by 43 calcium binding epidermal growth factor-like (cbEGF) 3 domains, tandem repeats of which are separated by transforming growth factor ␤-binding protein-like (TB) domains. Mutations in the fibrillin-1 gene (FBN1) give rise to the connective tissue disease Marfan syndrome and related disorders.In elastic tissues such as arteries, lung, and elastic ligaments, fibrillin microfibrils appear attached to cell membranes. These areas of attachment resemble focal contacts with an abundance of actin microfilaments on the cytoplasmic side of the membrane. Clustering of microfilaments at the cell surface at points of contact with the microfibrils suggest that microfibrillar components interact with cell-surface receptors which in turn serve as a dynamic link between cells and their microenvironment (2, 3).Fibrillin-1 is one of the microfibrillar proteins shown to mediate cell adhesion through binding to heterodimeric cell surface receptors of the integrin family (4, 5). This binding is at least in part mediated by the TB4 domain that contains an RGD (Arg-Gly-Asp) motif, a minimal integrin binding motif found in a number of extracellular matrix proteins. Fibrillin-integrin interactions are likely to be particularly important in tissues where microfibrils are in close proximity to cells, such as in the elastic lamellae, and may play a role in the assembly of the microfibril network, as has been shown in the case of fibronectin fibrillogenesis (6). Furthermore, the loss of cell-matrix interactions is likely to underlie some of the pleiotropic manifestations of Ma...

show abstract

Section: Discussionmentioning

confidence: 99%

αVβ6 Is a Novel Receptor for Human Fibrillin-1

Jovanović¹,

Takagi²,

Choulier³

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Although both collagen and elastin contribute to the mechanical response of the tissue (Holzapfel, 2008) we chose to digest collagen. The more complex elastin network is difficult to synthesize from scratch and a lack of elastin is a leading cause of graft failure in vivo due to compliance mismatch (Greenwald and Berry, 2000, Patel et al, 2006, Lee et al, 2011. A scaffold without an elastin network would not provide the elastic response necessary to match a native artery and is therefore essential for any vascular graft to have a fully matured elastin network (Lee et al, 2011, Fonck et al, 2007.…”

Section: Discussionmentioning

confidence: 99%

“…Elastin fibers organize into concentric sheets of elastic lamellae within the vessel wall and provide the elasticity to the vessel which is essential for compliance. The natural intricate structure of the elastic lamellae and its interaction with collagen and SMCs has resulted in few constructs expressing mature elastin in its native configuration (Dahl et al, 2007, Patel et al, 2006). This is a major limitation in tissue engineering vascular grafts as compliance mismatch in vivo is one of the main failure modes for implanted constructs (Kakisis et al, 2005, Wang et al, 2007.…”

Section: Introductionmentioning

confidence: 99%

Mechanical characterization of a customized decellularized scaffold for vascular tissue engineering

Sheridan

Duffy

Murphy

2012

Journal of the Mechanical Behavior of Biomedical Materials

View full text Add to dashboard Cite

“…The new frontiers of vascular engineering elastic recoil (74). In arteries, elastin dictates tissue mechanics at low strains before stiffer collagen fibers are engaged.…”

Section: Elastin Into Scaffolds: the Keystone Of Tevgsmentioning

confidence: 99%

Bioengineered Vascular Scaffolds: The State of the Art

et al. 2014

View full text Add to dashboard Cite

To date, there is increasing clinical need for vascular substitutes due to accidents, malformations, and ischemic diseases. Over the years, many approaches have been developed to solve this problem, starting from autologous native vessels to artificial vascular grafts; unfortunately, none of these have provided the perfect vascular substitute. All have been burdened by various complications, including infection, thrombogenicity, calcification, foreign body reaction, lack of growth potential, late stenosis and occlusion from intimal hyperplasia, and pseudoaneurysm formation. In the last few years, vascular tissue engineering has emerged as one of the most promising approaches for producing mechanically competent vascular substitutes. Nanotechnologies have contributed their part, allowing extraordinarily biostable and biocompatible materials to be developed. Specifically, the use of electrospinning to manufacture conduits able to guarantee a stable flow of biological fluids and guide the formation of a new vessel has revolutionized the concept of the vascular substitute. The electrospinning technique allows extracellular matrix (ECM) to be mimicked with high fidelity, reproducing its porosity and complexity, and providing an environment suitable for cell growth. In the future, a better knowledge of ECM and the manufacture of new materials will allow us to “create” functional biological vessels - the base required to develop organ substitutes and eventually solve the problem of organ failure.

show abstract

Elastin biosynthesis: The missing link in tissue-engineered blood vessels

Cited by 286 publications

References 96 publications

αVβ6 Is a Novel Receptor for Human Fibrillin-1

αVβ6 Is a Novel Receptor for Human Fibrillin-1

Mechanical characterization of a customized decellularized scaffold for vascular tissue engineering

Bioengineered Vascular Scaffolds: The State of the Art

Contact Info

Product

Resources

About