scholarly journals Regulation of limb patterning by extracellular microfibrils

2001 ◽  
Vol 154 (2) ◽  
pp. 275-282 ◽  
Author(s):  
Emilio Arteaga-Solis ◽  
Barbara Gayraud ◽  
Sui Y. Lee ◽  
Lillian Shum ◽  
Lynn Sakai ◽  
...  
Keyword(s):  
Elastic Fiber ◽  
Functional Interaction ◽  
Limb Patterning ◽  
Soluble Factors ◽  
Fiber Network ◽  
Patterning Defect ◽  
Interdigital Cell Death ◽  
Interdigital Tissues ◽  
Vertebrate Organogenesis ◽  
Lines Of Evidence

To elucidate the contribution of the extracellular microfibril–elastic fiber network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)–null mice by gene targeting and identified a limb-patterning defect in the form of bilateral syndactyly. Digit fusion involves both soft and hard tissues, and is associated with reduced apoptosis at affected sites. Two lines of evidence suggest that syndactily is primarily due to defective mesenchyme differentiation, rather than reduced apoptosis of interdigital tissue. First, fusion occurs before appearance of interdigital cell death; second, interdigital tissues having incomplete separation fail to respond to apoptotic clues from implanted BMP-4 beads. Syndactyly is associated with a disorganized matrix, but with normal BMP gene expression. On the other hand, mice double heterozygous for null Fbn2 and Bmp7 alleles display the combined digit phenotype of both nullizygotes. Together, these results imply functional interaction between Fbn2-rich microfibrils and BMP-7 signaling. As such, they uncover an unexpected relationship between the insoluble matrix and soluble factors during limb patterning. We also demonstrate that the Fbn2- null mutation is allelic to the recessive shaker-with-syndactyly (sy) locus on chromosome 18.

scholarly journals Elastic Fibers and Large Artery Mechanics in Animal Models of Development and Disease

2018 ◽  
Vol 140 (2) ◽  
Author(s):  
Maria Gabriela Espinosa ◽  
Marius Catalin Staiculescu ◽  
Jungsil Kim ◽  
Eric Marin ◽  
Jessica E. Wagenseil
Keyword(s):  
Animal Models ◽  
Mechanical Behavior ◽  
Computational Models ◽  
Mechanical Response ◽  
Elastic Fiber ◽  
High Stress ◽  
Elastic Fibers ◽  
Large Artery ◽  
Fiber Network ◽  
Pulsatile Pressure

Development of a closed circulatory system requires that large arteries adapt to the mechanical demands of high, pulsatile pressure. Elastin and collagen uniquely address these design criteria in the low and high stress regimes, resulting in a nonlinear mechanical response. Elastin is the core component of elastic fibers, which provide the artery wall with energy storage and recoil. The integrity of the elastic fiber network is affected by component insufficiency or disorganization, leading to an array of vascular pathologies and compromised mechanical behavior. In this review, we discuss how elastic fibers are formed and how they adapt in development and disease. We discuss elastic fiber contributions to arterial mechanical behavior and remodeling. We primarily present data from mouse models with elastic fiber deficiencies, but suggest that alternate small animal models may have unique experimental advantages and the potential to provide new insights. Advanced ultrastructural and biomechanical data are constantly being used to update computational models of arterial mechanics. We discuss the progression from early phenomenological models to microstructurally motivated strain energy functions for both collagen and elastic fiber networks. Although many current models individually account for arterial adaptation, complex geometries, and fluid–solid interactions (FSIs), future models will need to include an even greater number of factors and interactions in the complex system. Among these factors, we identify the need to revisit the role of time dependence and axial growth and remodeling in large artery mechanics, especially in cardiovascular diseases that affect the mechanical integrity of the elastic fibers.

Recent updates on the molecular network of elastic fiber formation

2019 ◽  
Vol 63 (3) ◽  
pp. 365-376 ◽  
Author(s):  
Seung Jae Shin ◽  
Hiromi Yanagisawa
Keyword(s):  
Elastic Fiber ◽  
Building Blocks ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Fiber Network ◽  
Associated Proteins ◽  
Fibrillin 1 ◽  
A Cell ◽  
Self Aggregation

Abstract Elastic fibers confer elasticity and recoiling to tissues and organs and play an essential role in induction of biochemical responses in a cell against mechanical forces derived from the microenvironment. The core component of elastic fibers is elastin (ELN), which is secreted as the monomer tropoelastin from elastogenic cells, and undergoes self-aggregation, cross-linking and deposition on to microfibrils, and assemble into insoluble ELN polymers. For elastic fibers to form, a microfibril scaffold (primarily formed by fibrillin-1 (FBN1)) is required. Numerous elastic fiber-associated proteins are involved in each step of elastogenesis and they instruct and/or facilitate the elastogenesis processes. In this review, we designated five proteins as key molecules in elastic fiber formation, including ELN, FBN1, fibulin-4 (FBLN4), fibulin-5 (FBLN5), and latent TGFβ-binding protein-4 (LTBP4). ELN and FBN1 serve as building blocks for elastic fibers. FBLN5, FBLN4 and LTBP4 have been demonstrated to play crucial roles in elastogenesis through knockout studies in mice. Using these molecules as a platform and expanding the elastic fiber network through the generation of an interactome map, we provide a concise review of elastogenesis with a recent update as well as discuss various biological functions of elastic fiber-associated proteins beyond elastogenesis in vivo.

scholarly journals Vascular Extracellular Matrix and Arterial Mechanics

2009 ◽  
Vol 89 (3) ◽  
pp. 957-989 ◽  
Author(s):  
Jessica E. Wagenseil ◽  
Robert P. Mecham
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Vessel Wall ◽  
Vascular System ◽  
Elastic Fiber ◽  
Circulatory System ◽  
Proper Function ◽  
Wall Structure ◽  
Fiber Network ◽  
Mechanical Models

An important factor in the transition from an open to a closed circulatory system was a change in vessel wall structure and composition that enabled the large arteries to store and release energy during the cardiac cycle. The component of the arterial wall in vertebrates that accounts for these properties is the elastic fiber network organized by medial smooth muscle. Beginning with the onset of pulsatile blood flow in the developing aorta, smooth muscle cells in the vessel wall produce a complex extracellular matrix (ECM) that will ultimately define the mechanical properties that are critical for proper function of the adult vascular system. This review discusses the structural ECM proteins in the vertebrate aortic wall and will explore how the choice of ECM components has changed through evolution as the cardiovascular system became more advanced and pulse pressure increased. By correlating vessel mechanics with physiological blood pressure across animal species and in mice with altered vessel compliance, we show that cardiac and vascular development are physiologically coupled, and we provide evidence for a universal elastic modulus that controls the parameters of ECM deposition in vessel wall development. We also discuss mechanical models that can be used to design better tissue-engineered vessels and to test the efficacy of clinical treatments.

scholarly journals Distribution of the large aggregating proteoglycan versican in adult human tissues.

1996 ◽  
Vol 44 (4) ◽  
pp. 303-312 ◽  
Author(s):  
B Bode-Lesniewska ◽  
M T Dours-Zimmermann ◽  
B F Odermatt ◽  
J Briner ◽  
P U Heitz ◽  
...  
Keyword(s):  
Core Protein ◽  
Splice Variants ◽  
Polyclonal Antibodies ◽  
Elastic Fiber ◽  
Basal Layer ◽  
Human Tissues ◽  
Connective Tissues ◽  
Fiber Network ◽  
Muscle Tissues ◽  
The Media

We studied the distribution of the large hyaluronan-binding proteoglycan versican (also known as PG-M) in human adult tissues using affinity-purified polyclonal antibodies that recognize the core protein of the prominent versican splice variants VO and V1. Versican was present in the loose connective tissues of various organs and was often associated with the elastic fiber network. Furthermore, it was localized in most smooth muscle tissues and in fibrous and elastic cartilage. Versican staining was also noted in the central and peripheral nervous system, in the basal layer of the epidermis, and on the luminal surface of some glandular epithelia. In blood vessels, versican was present in all three wall layers of veins and elastic arteries. In muscular arteries the immunoreactivity was normally restricted to the tunica adventitia. However, it appeared in the media and the split elastica interna of atherosclerotically transformed vessel walls. Our survey of the distribution of versican in normal human tissues now forms the basis for extended studies of potentially aberrant versican expression during pathogenic processes.

ELASTIC FIBER NETWORK OF THE LOWER EYELIDS

1996 ◽  
Vol 89 (Supplement) ◽  
pp. S74
Author(s):  
Angela F. Perry
Keyword(s):  
Elastic Fiber ◽  
Fiber Network

scholarly journals Predicting Proteolysis in Complex Proteomes Using Deep Learning

2021 ◽  
Vol 22 (6) ◽  
pp. 3071
Author(s):  
Matiss Ozols ◽  
Alexander Eckersley ◽  
Christopher I. Platt ◽  
Callum Stewart-McGuinness ◽  
Sarah A. Hibbert ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Cleavage Site ◽  
Prediction Models ◽  
Dermal Fibroblast ◽  
Elastic Fiber ◽  
Composition Analysis ◽  
Cleavage Sites ◽  
Fiber Network

Both protease- and reactive oxygen species (ROS)-mediated proteolysis are thought to be key effectors of tissue remodeling. We have previously shown that comparison of amino acid composition can predict the differential susceptibilities of proteins to photo-oxidation. However, predicting protein susceptibility to endogenous proteases remains challenging. Here, we aim to develop bioinformatics tools to (i) predict cleavage site locations (and hence putative protein susceptibilities) and (ii) compare the predicted vulnerabilities of skin proteins to protease- and ROS-mediated proteolysis. The first goal of this study was to experimentally evaluate the ability of existing protease cleavage site prediction models (PROSPER and DeepCleave) to identify experimentally determined MMP9 cleavage sites in two purified proteins and in a complex human dermal fibroblast-derived extracellular matrix (ECM) proteome. We subsequently developed deep bidirectional recurrent neural network (BRNN) models to predict cleavage sites for 14 tissue proteases. The predictions of the new models were tested against experimental datasets and combined with amino acid composition analysis (to predict ultraviolet radiation (UVR)/ROS susceptibility) in a new web app: the Manchester proteome susceptibility calculator (MPSC). The BRNN models performed better in predicting cleavage sites in native dermal ECM proteins than existing models (DeepCleave and PROSPER), and application of MPSC to the skin proteome suggests that: compared with the elastic fiber network, fibrillar collagens may be susceptible primarily to protease-mediated proteolysis. We also identify additional putative targets of oxidative damage (dermatopontin, fibulins and defensins) and protease action (laminins and nidogen). MPSC has the potential to identify potential targets of proteolysis in disparate tissues and disease states.

scholarly journals Studies in Cutaneous Aging: I. The Elastic Fiber Network

1982 ◽  
Vol 78 (5) ◽  
pp. 434-443 ◽  
Author(s):  
Irwin M. Braverman ◽  
Eileen Fonferko
Keyword(s):  
Elastic Fiber ◽  
Fiber Network

Elastic Fiber Fragmentation Increases Transmural Hydraulic Conductance and Solute Transport in Mouse Arteries

2018 ◽  
Vol 141 (2) ◽  
Author(s):  
Austin J. Cocciolone ◽  
Elizabeth O. Johnson ◽  
Jin-Yu Shao ◽  
Jessica E. Wagenseil
Keyword(s):  
Transport Properties ◽  
Ex Vivo ◽  
Elastic Fiber ◽  
Hydraulic Conductance ◽  
Solute Flux ◽  
Advective Transport ◽  
Wild Type ◽  
Fiber Network ◽  
Fiber Assembly ◽  
Solute Fluxes

Transmural advective transport of solute and fluid was investigated in mouse carotid arteries with either a genetic knockout of fibulin-5 (Fbln5−/−) or treatment with elastase to determine the influence of a disrupted elastic fiber matrix on wall transport properties. Fibulin-5 is an important director of elastic fiber assembly. Arteries from Fbln5−/− mice have a loose, noncontinuous elastic fiber network and were hypothesized to have reduced resistance to advective transport. Experiments were carried out ex vivo at physiological pressure and axial stretch. Hydraulic conductance (LP) was measured to be 4.99 × 10−6±8.94 × 10−7, 3.18−5±1.13 × 10−5 (p < 0.01), and 3.57 × 10−5 ±1.77 × 10−5 (p < 0.01) mm·s−1·mmHg−1 for wild-type, Fbln5−/−, and elastase-treated carotids, respectively. Solute fluxes of 4, 70, and 150 kDa fluorescein isothiocyanate (FITC)-dextran were statistically increased in Fbln5−/− compared to wild-type by a factor of 4, 22, and 3, respectively. Similarly, elastase-treated carotids demonstrated a 27- and 13-fold increase in net solute flux of 70 and 150 kDa FITC-dextran, respectively, compared to untreated carotids, and 4 kDa FITC-dextran was unchanged between these groups. Solute uptake of 4 and 70 kDa FITC-dextran within Fbln5−/− carotids was decreased compared to wild-type for all investigated time points. These changes in transport properties of elastic fiber compromised arteries have important implications for the kinetics of biomolecules and pharmaceuticals in arterial tissue following elastic fiber degradation due to aging or vascular disease.

scholarly journals Photodynamic Diagnosis and Treatment for Atherosclerosis by an Endoscopic Approach

1999 ◽  
Vol 5 (3) ◽  
pp. 191-195 ◽  
Author(s):  
Junichi Hayashi ◽  
Takashi Saito ◽  
Katsuo Aizawa
Keyword(s):  
Fluorescence Spectra ◽  
Elastic Fiber ◽  
Beating Heart ◽  
Photodynamic Diagnosis ◽  
Atheromatous Plaque ◽  
Descending Thoracic Aorta ◽  
Photodynamic Treatment ◽  
Fiber Network ◽  
Ftir Microspectroscopy ◽  
Atheromatous Plaques

The photosensitizer, mono-L-aspartyl chlorin e6 (NPe6), specifically accumulates in the atheromatous plaque. We detected the fluorescence spectra of NPe6 emitted from atheromatous plaques on the descending thoracic aorta by an angioscopic approach using the animal model of atherosclerosis. We also showed that a fluorescence spectrum peak at 675 nm was obtained laparoscopically only in parts of the abdominal aorta with an atheromatous plaque. By a fluorescence endoscope, atheromatous plaques on the carotid artery were recognized as reddish spots from outside the artery. In addition, we visualized specifically at the beating heart surface small coronary atherosclerosis using an epifluorescence stereoscope system.We examined the effects of photodynamic treatment with NPe6 on the atheromatous plaque. The change in the elastic framework in the atheromatous plaque after photodynamic treatment was evaluated using scanning electron microscopy. The destruction of the architecture of the elastic fiber network in the atheromatous plaque was revealed. We also studied the change in the lipid components of the atheromatous plaque using Fourier transform infrared (FTIR) microspectroscopy. FTIR microspectroscopic analysis showed a dissociation of ester bonds of cholesterol esters in the atheromatous plaque after photodynamic treatment. The framework of the atheromatous plaque and the lipids accumulated in the plaque could be destroyed following such treatment.

Sign in / Sign up

Export Citation Format

Share Document