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 Effects of Elastase Digestion on the Murine Vaginal Wall Biaxial Mechanical Response

2018 ◽  
Vol 141 (2) ◽  
Author(s):  
Akinjide R. Akintunde ◽  
Kathryn M. Robison ◽  
Daniel J. Capone ◽  
Laurephile Desrosiers ◽  
Leise R. Knoepp ◽  
...  
Keyword(s):  
Structural Integrity ◽  
Mechanical Response ◽  
Elastic Fiber ◽  
Pelvic Organ ◽  
Vaginal Wall ◽  
Elastic Fibers ◽  
Vaginal Tissue ◽  
Fiber Damage ◽  
Increased Risk ◽  
Before And After

Although the underlying mechanisms of pelvic organ prolapse (POP) remain unknown, disruption of elastic fiber metabolism within the vaginal wall extracellular matrix (ECM) has been highly implicated. It has been hypothesized that elastic fiber fragmentation correlates to decreased structural integrity and increased risk of prolapse; however, the mechanisms by which elastic fiber damage may contribute to prolapse are poorly understood. Furthermore, the role of elastic fibers in normal vaginal wall mechanics has not been fully ascertained. Therefore, the objective of this study is to investigate the contribution of elastic fibers to murine vaginal wall mechanics. Vaginal tissue from C57BL/6 female mice was mechanically tested using biaxial extension–inflation protocols before and after intraluminal exposure to elastase. Elastase digestion induced marked changes in the vaginal geometry, and biaxial mechanical properties, suggesting that elastic fibers may play an important role in vaginal wall mechanical function. Additionally, a constitutive model that considered two diagonal families of collagen fibers with a slight preference toward the circumferential direction described the data reasonably well before and after digestion. The present findings may be important to determine the underlying structural and mechanical mechanisms of POP, and aid in the development of growth and remodeling models for improved assessment and prediction of changes in structure–function relationships with prolapse development.

Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences

2008 ◽  
Vol 105 (5) ◽  
pp. 1643-1651 ◽  
Author(s):  
Jeffrey Atkinson
Keyword(s):  
Animal Models ◽  
Vascular Calcification ◽  
Arterial Wall ◽  
Elastic Fiber ◽  
Calcium Content ◽  
Laboratory Animals ◽  
Arterial Calcification ◽  
Fiber Network ◽  
Age Related ◽  
Wall Stiffness

With age, the calcium content of the arterial wall increases. Calcification occurs at two main levels: intimal plaques and the medial elastic fiber network. The latter has been referred to as medial elastocalcinosis and is the subject of this review. The mechanisms involved in elastocalcinosis are complex and involve polar, apolar, and active processes. Vascular calcification may be species specific to humans. As laboratory animals, such as the rat, grow old, they suffer from only very mild arterial calcification. Different animal models of induction of massive arterial calcification by pharmacological and other means exist. Although extrapolation from such models to the clinical situation in terms of etiology is difficult, such models could be useful in the nonclinical study of the pathophysiological consequences of vascular calcification. Vascular calcification modifies arterial wall stiffness, and this could have clinically significant consequences on cardiac function and downstream circulatory control.

scholarly journals Role of LTBP4 in alveolarization, angiogenesis, and fibrosis in lungs

2017 ◽  
Vol 313 (4) ◽  
pp. L687-L698 ◽  
Author(s):  
Insa Bultmann-Mellin ◽  
Katharina Dinger ◽  
Carolin Debuschewitz ◽  
Katharina M. A. Loewe ◽  
Yvonne Melcher ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Elastic Fiber ◽  
Transforming Growth Factor Β ◽  
Matrix Proteins ◽  
Extracellular Matrix Protein ◽  
Elastic Fibers ◽  
Fiber Network

Deficiency of the extracellular matrix protein latent transforming growth factor-β (TGF-β)-binding protein-4 (LTBP4) results in lack of intact elastic fibers, which leads to disturbed pulmonary development and lack of normal alveolarization in humans and mice. Formation of alveoli and alveolar septation in pulmonary development requires the concerted interaction of extracellular matrix proteins, growth factors such as TGF-β, fibroblasts, and myofibroblasts to promote elastogenesis as well as vascular formation in the alveolar septae. To investigate the role of LTBP4 in this context, lungs of LTBP4-deficient ( Ltbp4−/−) mice were analyzed in close detail. We elucidate the role of LTBP4 in pulmonary alveolarization and show that three different, interacting mechanisms might contribute to alveolar septation defects in Ltbp4−/− lungs: 1) absence of an intact elastic fiber network, 2) reduced angiogenesis, and 3) upregulation of TGF-β activity resulting in profibrotic processes in the lung.

scholarly journals Elastic Laminar Reorganization Occurs with Outward Diameter Oxidase for Stabilization

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 7
Author(s):  
Ryan M. McEnaney ◽  
Dylan D. McCreary ◽  
Nolan O. Skirtich ◽  
Elizabeth A. Andraska ◽  
Ulka Sachdev ◽  
...  
Keyword(s):  
Structural Changes ◽  
Elastic Fiber ◽  
Multiphoton Microscopy ◽  
Fold Increase ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Large Artery ◽  
Internal Elastic Lamina ◽  
Luminal Diameter ◽  
Collateral Arteries

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that deconstruction of the extracellular matrix is essential to remodel smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of internal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content was low. Outward remodeling of these vessels with a 10–20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension, as demonstrated by the straightening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

scholarly journals Elastic Laminar Reorganization Occurs with Outward Diameter Expansion during Collateral Artery Growth and Requires Lysyl Oxidase for Stabilization

2021 ◽  
Author(s):  
Ryan M McEnaney ◽  
Dylan D McCreary ◽  
Nolan Skirtich ◽  
Elizabeth Andraska ◽  
Ulka Sachdev ◽  
...  
Keyword(s):  
Structural Changes ◽  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Multiphoton Microscopy ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Large Artery ◽  
Luminal Diameter ◽  
Collateral Arteries ◽  
Collateral Artery

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

scholarly journals Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation

2013 ◽  
Vol 304 (5) ◽  
pp. H674-H686 ◽  
Author(s):  
William Wan ◽  
Rudolph L. Gleason
Keyword(s):  
Parameter Estimation ◽  
Mechanical Behavior ◽  
Carotid Arteries ◽  
Mechanical Response ◽  
Fiber Formation ◽  
Aortic Aneurysms ◽  
Elastic Fibers ◽  
Wild Type ◽  
Growth And Remodeling ◽  
Biaxial Tests

Elastin fragmentation is a common characteristic of vascular diseases, such as abdominal aortic aneurysms, peripheral arterial disease, and aortic dissection. Examining growth and remodeling in the presence of dysfunctional elastic fibers provides insight into the adaptive or maladaptive changes that tissues undergo in compensating for structural deficiencies. This study used the maturation of fibulin-5 knockout (KO) and wild-type mice to study the effects of fragmented elastic fibers on the growth and remodeling of carotid arteries. The microstructural content and organization and the biaxial mechanical behavior of common carotid arteries were measured, and parameter estimation performed from KO and WT mice aged 3, 4, 8, and 13 wk. Gross measurements and biaxial tests revealed significant differences in pressure-diameter behavior, in vivo axial stretch, opening angle, compliance, and wall stresses during maturation of wild-type arteries, but little change in these values in KO mice. Multiphoton microscopy used to image collagen fibers across the vessel wall in pressurized and stretched arteries suggests that there is little variation in fiber angles between different ages. Parameter estimation revealed significant differences in material parameters between genotypes and age groups. This study suggests that neonatal formation and cross-linking of functional elastic fibers, followed by increases in artery size due to growth with little remodeling of the elastic fibers, endow arteries with large distensibility and contribute to the evolution of mechanical behavior of arteries during maturation. Dysfunction in neonatal formation of elastic fibers abrogates many of the changes in mechanical response that take place during the maturation.

scholarly journals Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akira Minami ◽  
Yuka Fujita ◽  
Jun Goto ◽  
Ayano Iuchi ◽  
Kosei Fujita ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Skin Diseases ◽  
Lower Layer ◽  
Elastic Fiber ◽  
Sialic Acid Residue ◽  
Elastic Fibers ◽  
Transdermal Administration ◽  
Sialidase Activity ◽  
Fiber Assembly ◽  
Senescence Accelerated Mice

AbstractReduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.

scholarly journals Clinical Relevance of Elastin in the Structure and Function of Skin

2021 ◽  
Author(s):  
Leslie Baumann ◽  
Eric F Bernstein ◽  
Anthony S Weiss ◽  
Damien Bates ◽  
Shannon Humphrey ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Relevance ◽  
Structural Integrity ◽  
Elastic Fiber ◽  
Subcutaneous Fat ◽  
Structure And Function ◽  
Fiber Formation ◽  
Elastic Fibers ◽  
Superficial Dermis ◽  
And Function

Abstract Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

scholarly journals Dill Extract Induces Elastic Fiber Neosynthesis and Functional Improvement in the Ascending Aorta of Aged Mice with Reversal of Age-Dependent Cardiac Hypertrophy and Involvement of Lysyl Oxidase-Like-1

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 173 ◽  
Author(s):  
Wassim Fhayli ◽  
Quentin Boëté ◽  
Nadjib Kihal ◽  
Valérie Cenizo ◽  
Pascal Sommer ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Lysyl Oxidase ◽  
Elastic Fiber ◽  
Ascending Aorta ◽  
Functional Improvement ◽  
Elastic Fibers ◽  
Aged Mice ◽  
Age Related ◽  
And Function

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin fibroblasts to increase lysyl oxidase–like-1 (LOXL-1) gene expression, an enzyme contributing to tropoelastin crosslinking and elastin formation. Here, we have investigated the effects of a chronic treatment (three months) of aged male mice with DE (5% or 10% v/v, in drinking water) on the structure and function of the ascending aorta. DE treatment, especially at 10%, of aged mice protected pre-existing elastic lamellae, reactivated tropoelastin and LOXL-1 expressions, induced elastic fiber neo-synthesis, and decreased the stiffness of the aging aortic wall, probably explaining the reversal of the age-related cardiac hypertrophy also observed following the treatment. DE could thus be considered as an anti-aging product for the cardiovascular system.

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