-
The FEBS Journal Aug 2019The Cardiovascular Continuum describes a sequence of events from cardiovascular risk factors to end-stage heart disease. It includes conventional pathologies affecting... (Review)
Review
The Cardiovascular Continuum describes a sequence of events from cardiovascular risk factors to end-stage heart disease. It includes conventional pathologies affecting cardiovascular functions such as hypertension, atherosclerosis or thrombosis and was traditionally considered from the metabolic point of view. This Cardiovascular Continuum, originally described by Dzau and Braunwald, was extended by O'Rourke to consider also the crucial role played by degradation of elastic fibers, occurring during aging, in the appearance of vascular stiffness, another deleterious risk factor of the continuum. However, the involvement of the elastin degradation products, named elastin-derived peptides, to the Cardiovascular Continuum progression has not been considered before. Data from our laboratory and others clearly showed that these bioactive peptides are central regulators of this continuum, thereby amplifying appearance and evolution of cardiovascular risk factors such as diabetes or hypertension, of vascular alterations such as atherothrombosis and calcification, but also nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The Elastin Receptor Complex has been shown to be a crucial actor in these processes. We propose here the participation of these elastin-derived peptides and of the Elastin Receptor Complex in these events, and introduce a revisited Cardiovascular Continuum based on their involvement, for which elastin-based pharmacological strategies could have a strong impact in the future.
Topics: Animals; Cardiovascular Diseases; Elastin; Humans; Metabolic Syndrome; Peptides; Receptors, Cell Surface
PubMed: 30946528
DOI: 10.1111/febs.14836 -
Matrix Biology : Journal of the... Nov 2018Elastin is expressed in most tissues that require elastic recoil. The protein first appeared coincident with the closed circulatory system, and was critical for the... (Review)
Review
Elastin is expressed in most tissues that require elastic recoil. The protein first appeared coincident with the closed circulatory system, and was critical for the evolutionary success of the vertebrate lineage. Elastin is expressed by multiple cell types in the lung, including mesothelial cells in the pleura, smooth muscle cells in airways and blood vessels, endothelial cells, and interstitial fibroblasts. This highly crosslinked protein associates with fibrillin-containing microfibrils to form the elastic fiber, which is the physiological structure that functions in the extracellular matrix. Elastic fibers can be woven into many different shapes depending on the mechanical needs of the tissue. In large pulmonary vessels, for example, elastin forms continuous sheets, or lamellae, that separate smooth muscle layers. Outside of the vasculature, elastic fibers form an extensive fiber network that originates in the central bronchi and inserts into the distal airspaces and visceral pleura. The fibrous cables form a looping system that encircle the alveolar ducts and terminal air spaces and ensures that applied force is transmitted equally to all parts of the lung. Normal lung function depends on proper secretion and assembly of elastin, and either inhibition of elastin fiber assembly or degradation of existing elastin results in lung dysfunction and disease.
Topics: Animals; Elastin; Extracellular Matrix; Humans; Lung; Lung Diseases
PubMed: 29331337
DOI: 10.1016/j.matbio.2018.01.005 -
Circulation Research Jan 2023Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to...
BACKGROUND
Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar. We sought to improve post-MI healing by introducing tropoelastin, the soluble subunit of elastin, to alter scar mechanics early after MI.
METHODS AND RESULTS
We developed an ultrasound-guided direct intramyocardial injection method to administer tropoelastin directly into the left ventricular anterior wall of rats subjected to induced MI. Experimental groups included shams and infarcted rats injected with either PBS vehicle control or tropoelastin. Compared to vehicle treated controls, echocardiography assessments showed tropoelastin significantly improved left ventricular ejection fraction (64.7±4.4% versus 46.0±3.1% control) and reduced left ventricular dyssynchrony (11.4±3.5 ms versus 31.1±5.8 ms control) 28 days post-MI. Additionally, tropoelastin reduced post-MI scar size (8.9±1.5% versus 20.9±2.7% control) and increased scar elastin (22±5.8% versus 6.2±1.5% control) as determined by histological assessments. RNA sequencing (RNAseq) analyses of rat infarcts showed that tropoelastin injection increased genes associated with elastic fiber formation 7 days post-MI and reduced genes associated with immune response 11 days post-MI. To show translational relevance, we performed immunohistochemical analyses on human ischemic heart disease cardiac samples and showed an increase in tropoelastin within fibrotic areas. Using RNA-seq we also demonstrated the tropoelastin gene is upregulated in human ischemic heart disease and during human cardiac fibroblast-myofibroblast differentiation. Furthermore, we showed by immunocytochemistry that human cardiac fibroblast synthesize increased elastin in direct response to tropoelastin treatment.
CONCLUSIONS
We demonstrate for the first time that purified human tropoelastin can significantly repair the infarcted heart in a rodent model of MI and that human cardiac fibroblast synthesize elastin. Since human cardiac fibroblasts are primarily responsible for post-MI scar synthesis, our findings suggest exciting future clinical translation options designed to therapeutically manipulate this synthesis.
Topics: Humans; Rats; Animals; Myocardium; Elastin; Tropoelastin; Cicatrix; Stroke Volume; Ventricular Function, Left; Myocardial Infarction; Myocytes, Cardiac; Collagen; Ventricular Remodeling
PubMed: 36453283
DOI: 10.1161/CIRCRESAHA.122.321123 -
Acta Biomaterialia Mar 2022Elastin-like polymers (ELPs) and their chimeric subfamily the silk elastin-like polymers (SELPs) exhibit a lower critical solvation temperature (LCST) behavior in water...
Elastin-like polymers (ELPs) and their chimeric subfamily the silk elastin-like polymers (SELPs) exhibit a lower critical solvation temperature (LCST) behavior in water which has been extensively studied from theoretical, computational and experimental perspectives. The inclusion of silk domains in the backbone of the ELPs effects the molecular dynamics of the elastin-like domains in response to increased temperature above its transition temperature and confers gelation ability. This response has been studied in terms of initial and long-term changes in structures, however, intermediate transition states have been less investigated. Moreover, little is known about the effects of reversible hydration on the elastin versus silk domains in the physical crosslinks. We used spectroscopic techniques to analyze initial, intermediate and long-term states of the crosslinks in SELPs. A combination of thermoanalytical and rheological measurements demonstrated that the fast reversible rehydration of the elastin motifs adjacent to the relatively small silk domains was capable of breaking the silk physical crosslinks. This feature can be exploited to tailor the dynamics of these types of crosslinks in SELPs. STATEMENT OF SIGNIFICANCE: The combination of silk and elastin in a single molecule results in synergy via their interactions to impact the protein polymer properties. The ability of the silk domains to crosslink affects the thermoresponsive properties of the elastin domains. These interactions have been studied at early and late states of the physical crosslinking, while the intermediate states were the focus of the present study to understand the reversible phase-transitions of the elastin domains over the silk physical crosslinking. The thermoresponsive properties of the elastin domains at the initial, intermediate and late states of silk crosslinking were characterized to demonstrate that reversible hydration of the elastin domains influenced the reversibility of the silk crosslinks.
Topics: Elastin; Hydrogels; Polymers; Silk; Temperature
PubMed: 34971785
DOI: 10.1016/j.actbio.2021.12.031 -
Cellular and Molecular Neurobiology Nov 2022Elastin is one of the main structural matrix proteins of the arteries, lung, cartilage, elastic ligaments, brain vessels, and skin. These elastin fibers display... (Review)
Review
Elastin is one of the main structural matrix proteins of the arteries, lung, cartilage, elastic ligaments, brain vessels, and skin. These elastin fibers display incredible resilience and structural stability with long half-life. However, during some physiological and pathophysiological conditions, elastin is prone to proteolytic degradation and, due to the extremely low turnover rate, its degradation is practically an irreversible and irreparable phenomenon. As a result of elastin degradation, new peptides called elastin-derived peptides (EDPs) are formed. A growing body of evidence suggests that these peptides play an important role in the development of age-related vascular disease. They are also detected in the cerebrospinal fluid of healthy people, and their amount increases in patients after ischemic stroke. Recently, elastin-like polypeptides have been reported to induce overproduction of beta-amyloid in a model of Alzheimer's disease. Nevertheless, the role and mechanism of action of EDPs in the nervous system is largely unknown and limited to only a few studies. The article summarizes the current state of knowledge on the role of EDPs in the nervous system.
Topics: Central Nervous System; Elastin; Humans; Peptides
PubMed: 34374904
DOI: 10.1007/s10571-021-01140-0 -
FEBS Letters Aug 1990A succinct overview of recent results on the biochemistry of extracellular matrix (ECM) is presented. The rapid expansion of this discipline over the best decades... (Review)
Review
A succinct overview of recent results on the biochemistry of extracellular matrix (ECM) is presented. The rapid expansion of this discipline over the best decades renders impossible to give an even approximately complete coverage of matrix biology. Some selected results concerning the four major families of macromolecules composing the ECM, that is, collagens (14 types described), elastin(s), proteoglycans and structural glycoproteins (especially fibronectin) are described. Special attention is directed to a crucial aspect of matrix biology: cell-matrix interactions. A number of cell membrane receptors were recently described mediating the two way information flow from the cells to the matrix via the 'programme' of ECM synthesis coded in the genome and unfolding during differentiation and from the ECM to the cells through the membrane receptors which contact the cytoskeleton. One of them at least, the elastin receptor was shown to be linked through a G-protein-phospholipase C-IP3 mediated relay to the regulation of intracellular calcium. Modifications of the ECM will therefore influence cell behaviour. Derangements of this informational feed back mechanisms appear to be involved in most age-related connective tissue diseases.
Topics: Animals; Calcium; Collagen; Elastin; Extracellular Matrix; Fibronectins; Glycoproteins; Proteoglycans; Receptors, Cell Surface
PubMed: 2166694
DOI: 10.1016/0014-5793(90)81291-u -
Matrix Biology : Journal of the... Mar 2013Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms... (Review)
Review
Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine-governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin-cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production.
Topics: Cell Cycle; Cyclins; Cytokines; Elastin; Fibroblast Growth Factors; Humans; Insulin-Like Growth Factor I; Proteolysis; Transforming Growth Factor beta1
PubMed: 23160093
DOI: 10.1016/j.matbio.2012.11.004 -
IUBMB Life May 2020Elastic fibers are essential assemblies of vertebrates and confer elasticity and resilience to various organs including blood vessels, lungs, skin, and ligaments. Mature... (Review)
Review
Elastic fibers are essential assemblies of vertebrates and confer elasticity and resilience to various organs including blood vessels, lungs, skin, and ligaments. Mature fibers, which comprise a dense and insoluble elastin core and a microfibrillar mantle, are extremely resistant toward intrinsic and extrinsic influences and maintain elastic function over the human lifespan in healthy conditions. The oxidative deamination of peptidyl lysine to peptidyl allysine in elastin's precursor tropoelastin is a crucial posttranslational step in their formation. The modification is catalyzed by members of the family of lysyl oxidases and the starting point for subsequent manifold condensation reactions that eventually lead to the highly cross-linked elastomer. This review summarizes the current understanding of the formation of cross-links within and between the monomer molecules, the molecular sites, and cross-link types involved and the pathological consequences of abnormalities in the cross-linking process.
Topics: 2-Aminoadipic Acid; Aging; Animals; Blood Vessels; Connective Tissue Diseases; Elastic Tissue; Elastin; Humans; Ligaments; Lung; Lysine; Microfibrils; Oxidation-Reduction; Protein Processing, Post-Translational; Protein-Lysine 6-Oxidase; Skin
PubMed: 31834666
DOI: 10.1002/iub.2213 -
Macromolecular Bioscience Aug 2022Genetically engineered silk-elastin-like-proteins (SELPs) synthesized with the combination of silk and elastin domains are bioengineered to also contain a graphene oxide...
Genetically engineered silk-elastin-like-proteins (SELPs) synthesized with the combination of silk and elastin domains are bioengineered to also contain a graphene oxide (GO) binding domain. The conductivity and mechanical stability of graphene, combined with SELP-specific graphene interfaces are pursued as dynamic hybrid materials, toward biomaterial-based electronic switches. The resulting bioengineered proteins with added GO demonstrate cytocompatibility and conductivity that could be modulated by changing hydrogel size in response to temperature due to the SELP chemistry. Upon increased temperature, the gels coalesce and contract, providing sufficient condensed spacing to facilitate conductivity via the graphene domains, a feature that is lost at lower temperatures with the more expanded hydrogels. This thermally induced contraction-expansion is reversible and cyclable, providing an "on-off" conductive switch driven by temperature-driven hydrogel shape-change.
Topics: Biocompatible Materials; Elastin; Electronics; Graphite; Hydrogels; Oxides; Silk
PubMed: 35634798
DOI: 10.1002/mabi.202200122 -
Experimental Biology and Medicine... May 2016Recent strides in the development of multifunctional synthetic biomimetic materials through the self-assembly of multi-domain peptides and proteins over the past decade... (Review)
Review
Recent strides in the development of multifunctional synthetic biomimetic materials through the self-assembly of multi-domain peptides and proteins over the past decade have been realized. Such engineered systems have wide-ranging application in bioengineering and medicine. This review focuses on fundamental fiber forming α-helical coiled-coil peptides, peptide amphiphiles, and amyloid-based self-assembling peptides; followed by higher order collagen- and elastin-mimetic peptides with an emphasis on chemical / biological characterization and biomimicry.
Topics: Amyloid; Animals; Biomimetic Materials; Collagen; Elastin; Humans; Peptides; Protein Conformation; Tissue Engineering
PubMed: 27022140
DOI: 10.1177/1535370216640941