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Matrix Biology : Journal of the... 2015Most abundant in the extracellular matrix are collagens, joined by elastin that confers elastic recoil to the lung, aorta, and skin. These fibrils are highly resistant... (Review)
Review
Most abundant in the extracellular matrix are collagens, joined by elastin that confers elastic recoil to the lung, aorta, and skin. These fibrils are highly resistant to proteolysis but can succumb to a minority of the matrix metalloproteinases (MMPs). Considerable inroads to understanding how such MMPs move to the susceptible sites in collagen and then unwind the triple helix of collagen monomers have been gained. The essential role in unwinding of the hemopexin-like domain of interstitial collagenases or the collagen binding domain of gelatinases is highlighted. Elastolysis is also facilitated by the collagen binding domain in the cases of MMP-2 and MMP-9, and remote exosites of the catalytic domain in the case of MMP-12.
Topics: Binding Sites; Collagen; Elastin; Humans; Matrix Metalloproteinases; Models, Molecular; Protein Binding; Protein Structure, Secondary; Proteolysis; Substrate Specificity
PubMed: 25599938
DOI: 10.1016/j.matbio.2015.01.005 -
Advanced Healthcare Materials Nov 2015The mechanical stability, elasticity, inherent bioactivity, and self-assembly properties of elastin make it a highly attractive candidate for the fabrication of... (Review)
Review
The mechanical stability, elasticity, inherent bioactivity, and self-assembly properties of elastin make it a highly attractive candidate for the fabrication of versatile biomaterials. The ability to engineer specific peptide sequences derived from elastin allows the precise control of these physicochemical and organizational characteristics, and further broadens the diversity of elastin-based applications. Elastin and elastin-like peptides can also be modified or blended with other natural or synthetic moieties, including peptides, proteins, polysaccharides, and polymers, to augment existing capabilities or confer additional architectural and biofunctional features to compositionally pure materials. Elastin and elastin-based composites have been subjected to diverse fabrication processes, including heating, electrospinning, wet spinning, solvent casting, freeze-drying, and cross-linking, for the manufacture of particles, fibers, gels, tubes, sheets and films. The resulting materials can be tailored to possess specific strength, elasticity, morphology, topography, porosity, wettability, surface charge, and bioactivity. This extraordinary tunability of elastin-based constructs enables their use in a range of biomedical and tissue engineering applications such as targeted drug delivery, cell encapsulation, vascular repair, nerve regeneration, wound healing, and dermal, cartilage, bone, and dental replacement.
Topics: Animals; Biocompatible Materials; Drug Delivery Systems; Elastin; Humans; Peptides; Protein Engineering; Tissue Scaffolds
PubMed: 25771993
DOI: 10.1002/adhm.201400781 -
Matrix Biology : Journal of the... Oct 2018Elastic fibers provide recoil to tissues that undergo repeated deformation, such as blood vessels, lungs and skin. Composed of elastin and its accessory proteins, the... (Review)
Review
Elastic fibers provide recoil to tissues that undergo repeated deformation, such as blood vessels, lungs and skin. Composed of elastin and its accessory proteins, the fibers are produced within a restricted developmental window and are stable for decades. Their eventual breakdown is associated with a loss of tissue resiliency and aging. Rare alteration of the elastin (ELN) gene produces disease by impacting protein dosage (supravalvar aortic stenosis, Williams Beuren syndrome and Williams Beuren region duplication syndrome) and protein function (autosomal dominant cutis laxa). This review highlights aspects of the elastin molecule and its assembly process that contribute to human disease and also discusses potential therapies aimed at treating diseases of elastin insufficiency.
Topics: Aortic Stenosis, Supravalvular; Cutis Laxa; Elastin; Gene Dosage; Genetic Predisposition to Disease; Humans; Mutation; Williams Syndrome
PubMed: 29501665
DOI: 10.1016/j.matbio.2018.02.021 -
Topics in Current Chemistry 2012Elastomeric polypeptides are very interesting biopolymers and are characterized by rubber-like elasticity, large extensibility before rupture, reversible deformation... (Review)
Review
Elastomeric polypeptides are very interesting biopolymers and are characterized by rubber-like elasticity, large extensibility before rupture, reversible deformation without loss of energy, and high resilience upon stretching. Their useful properties have motivated their use in a wide variety of materials and biological applications. This chapter focuses on elastin and resilin - two elastomeric biopolymers - and the recombinant polypeptides derived from them (elastin-like polypeptides and resilin-like polypeptides). This chapter also discusses the applications of these recombinant polypeptides in the fields of purification, drug delivery, and tissue engineering.
Topics: Amino Acid Sequence; Animals; Biocompatible Materials; Chromatography, Affinity; Delayed-Action Preparations; Drug Carriers; Elasticity; Elastin; Humans; Insect Proteins; Insecta; Molecular Sequence Data; Peptides; Phase Transition; Recombinant Proteins; Temperature; Tissue Engineering; Tropoelastin
PubMed: 21826606
DOI: 10.1007/128_2011_205 -
Journal of Pharmacy & Pharmaceutical... 2020Elastin is one of the main components of the extracellular matrix; it provides resistance and elasticity to a variety of tissues and organs of the human body, besides... (Review)
Review
Elastin is one of the main components of the extracellular matrix; it provides resistance and elasticity to a variety of tissues and organs of the human body, besides participating in cellular signaling. On the other hand, elastin-derived peptides are synthetic biopolymers with a similar conformation and structure to elastin, but these possess the advantage of solubility in aqueous mediums. Due to their biological activities and physicochemical properties, elastin and related peptides may be applied as biomaterials to develop diverse biomedical devices, including scaffolds, hydrogels, and drug delivery systems for tissue engineering. Likewise, the combination of elastin with natural or synthetic polymers has demonstrated to improve the mechanical properties of biomedical products and drug delivery systems. Here we comprehensively describe the physicochemical properties and physiological functions of elastin. Moreover, we offer an overview of the use of elastin and its derivative polymers as biomaterials to develop scaffolds and hydrogels for tissue engineering. Finally, we discuss some perspectives on the employment of these biopolymers to fabricate new biomedical products.
Topics: Biocompatible Materials; Drug Delivery Systems; Elastin; Humans; Hydrogels; Peptides; Tissue Engineering
PubMed: 33751927
DOI: 10.18433/jpps31254 -
American Journal of Physiology. Cell... Sep 2022Elastin provides recoil to tissues that stretch such as the lung, blood vessels, and skin. It is deposited in a brief window starting in the prenatal period and... (Review)
Review
Elastin provides recoil to tissues that stretch such as the lung, blood vessels, and skin. It is deposited in a brief window starting in the prenatal period and extending to adolescence in vertebrates, and then slowly turns over. Elastin insufficiency is seen in conditions such as Williams-Beuren syndrome and elastin-related supravalvar aortic stenosis, which are associated with a range of vascular and connective tissue manifestations. Regulation of the elastin () gene occurs at multiple levels including promoter activation/inhibition, mRNA stability, interaction with microRNAs, and alternative splicing. However, these mechanisms are incompletely understood. Better understanding of the processes controlling gene expression may improve medicine's ability to intervene in these rare conditions, as well as to replace age-associated losses by re-initiating elastin production. This review describes what is known about the gene promoter structure, transcriptional regulation by cytokines and transcription factors, and posttranscriptional regulation via mRNA stability and micro-RNA and highlights new approaches that may influence regenerative medicine.
Topics: Animals; Aortic Stenosis, Supravalvular; Elastin; Gene Expression Regulation; Humans; MicroRNAs; Williams Syndrome
PubMed: 35816641
DOI: 10.1152/ajpcell.00228.2022 -
American Journal of Physiology. Cell... May 2022Elastin is a long-lived extracellular matrix protein that is organized into elastic fibers that provide elasticity to the arterial wall, allowing stretch and recoil with... (Review)
Review
Elastin is a long-lived extracellular matrix protein that is organized into elastic fibers that provide elasticity to the arterial wall, allowing stretch and recoil with each cardiac cycle. By forming lamellar units with smooth muscle cells, elastic fibers transduce tissue-level mechanics to cell-level changes through mechanobiological signaling. Altered amounts or assembly of elastic fibers leads to changes in arterial structure and mechanical behavior that compromise cardiovascular function. In particular, genetic mutations in the elastin gene () that reduce elastin protein levels are associated with focal arterial stenosis, or narrowing of the arterial lumen, such as that seen in supravalvular aortic stenosis and Williams-Beuren syndrome. Global reduction of levels in mice allows investigation of the tissue- and cell-level arterial mechanical changes and associated alterations in smooth muscle cell phenotype that may contribute to stenosis formation. A loxP-floxed allele in mice highlights cell type- and developmental origin-specific mechanobiological effects of reduced elastin amounts. production is required in distinct cell types for elastic layer formation in different parts of the mouse vasculature. deletion in smooth muscle cells from different developmental origins in the ascending aorta leads to characteristic patterns of vascular stenosis and neointima. Dissecting the mechanobiological signaling associated with local depletion and subsequent smooth muscle cell response may help develop new therapeutic interventions for elastin-related diseases.
Topics: Animals; Aorta; Arteries; Constriction, Pathologic; Elastin; Mice; Myocytes, Smooth Muscle
PubMed: 35196168
DOI: 10.1152/ajpcell.00448.2021 -
The Journal of Clinical Investigation Mar 2022Obstructive arterial diseases, including supravalvular aortic stenosis (SVAS), atherosclerosis, and restenosis, share 2 important features: an abnormal or disrupted...
Obstructive arterial diseases, including supravalvular aortic stenosis (SVAS), atherosclerosis, and restenosis, share 2 important features: an abnormal or disrupted elastic lamellae structure and excessive smooth muscle cells (SMCs). However, the relationship between these pathological features is poorly delineated. SVAS is caused by heterozygous loss-of-function, hypomorphic, or deletion mutations in the elastin gene (ELN), and SVAS patients and elastin-mutant mice display increased arterial wall cellularity and luminal obstructions. Pharmacological treatments for SVAS are lacking, as the underlying pathobiology is inadequately defined. Herein, using human aortic vascular cells, mouse models, and aortic samples and SMCs derived from induced pluripotent stem cells of ELN-deficient patients, we demonstrated that elastin insufficiency induced epigenetic changes, upregulating the NOTCH pathway in SMCs. Specifically, reduced elastin increased levels of γ-secretase, activated NOTCH3 intracellular domain, and downstream genes. Notch3 deletion or pharmacological inhibition of γ-secretase attenuated aortic hypermuscularization and stenosis in Eln-/- mutants. Eln-/- mice expressed higher levels of NOTCH ligand JAGGED1 (JAG1) in aortic SMCs and endothelial cells (ECs). Finally, Jag1 deletion in SMCs, but not ECs, mitigated the hypermuscular and stenotic phenotype in the aorta of Eln-/- mice. Our findings reveal that NOTCH3 pathway upregulation induced pathological aortic SMC accumulation during elastin insufficiency and provide potential therapeutic targets for SVAS.
Topics: Amyloid Precursor Protein Secretases; Animals; Aorta; Aortic Stenosis, Supravalvular; Constriction, Pathologic; Elastin; Endothelial Cells; Humans; Jagged-1 Protein; Mice; Receptor, Notch3
PubMed: 34990407
DOI: 10.1172/JCI142338 -
American Journal of Physiology. Heart... Aug 2018Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein... (Review)
Review
Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein responsible for this reversible elasticity that reduces the workload on the heart and dampens pulsatile flow in distal arteries. Here, we summarize the elastin protein biochemistry, self-association behavior, cross-linking process, and multistep elastic fiber assembly that provide large arteries with their unique mechanical properties. We present measures of passive arterial mechanics that depend on elastic fiber amounts and integrity such as the Windkessel effect, structural and material stiffness, and energy storage. We discuss supravalvular aortic stenosis and autosomal dominant cutis laxa-1, which are genetic disorders caused by mutations in the elastin gene. We present mouse models of supravalvular aortic stenosis, autosomal dominant cutis laxa-1, and graded elastin amounts that have been invaluable for understanding the role of elastin in arterial mechanics and cardiovascular disease. We summarize acquired diseases associated with elastic fiber defects, including hypertension and arterial stiffness, diabetes, obesity, atherosclerosis, calcification, and aneurysms and dissections. We mention animal models that have helped delineate the role of elastic fiber defects in these acquired diseases. We briefly summarize challenges and recent advances in generating functional elastic fibers in tissue-engineered arteries. We conclude with suggestions for future research and opportunities for therapeutic intervention in genetic and acquired elastinopathies.
Topics: Animals; Biomechanical Phenomena; Cardiovascular Diseases; Coronary Vessels; Elastin; Humans
PubMed: 29631368
DOI: 10.1152/ajpheart.00087.2018 -
Matrix Biology : Journal of the... Nov 2019Studies over the years have described a filamentous structure to mature elastin that suggests a complicated packing arrangement of tropoelastin subunits. The currently... (Review)
Review
Studies over the years have described a filamentous structure to mature elastin that suggests a complicated packing arrangement of tropoelastin subunits. The currently accepted mechanism for tropoelastin assembly requires microfibrils to serve as a physical extracellular scaffold for alignment of tropoelastin monomers during and before crosslinking. However, recent evidence suggests that the initial stages of tropoelastin assembly occur within the cell or at unique assembly sites on the plasma membrane where tropoelastin self assembles to form elastin aggregates. Outside the cell, elastin aggregates transfer to growing elastic fibers in the extracellular matrix where tensional forces on microfibrils generated through cell movement help shape the growing fiber. Overall, these observations challenge the widely held idea that interaction between monomeric tropoelastin and microfibrils is a requirement for elastin assembly, and point to self-assembly of tropoelastin as a driving force in elastin maturation.
Topics: Animals; Cell Movement; Elastin; Extracellular Matrix; Humans; Protein Multimerization; Tropoelastin
PubMed: 31669522
DOI: 10.1016/j.matbio.2019.10.002