Elastin in healthy and diseased lung

Vindin, Howard; Oliver, Brian G.; Weiss, Anthony S.

doi:10.1016/j.copbio.2021.10.025

Cited by 11 publications

(7 citation statements)

References 69 publications

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“…For example, emphysema and cystic fibrosis exhibit targeted elastin damage, activating the body’s physiological response to compensate through the addition of collagen fibers [ 15 , 16 , 17 ]. Paradoxically, fiber deposition strengthens the vulnerable areas, but leads to tissue stiffening, and decreases lung compliance [ 18 , 19 , 20 ]. This remodeling of the connective tissue network induces heterogeneity that exacerbates ventilator injuries, atelectasis, and other mechanical changes such as increased resistance and heightened strains in the lungs [ 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

et al. 2023

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Background Common respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date. Methods Specimens were extracted from the proximal and distal airways, namely the trachea, large bronchi, and small bronchi to facilitate evaluations of material heterogeneity, and subjected to biaxial planar loading in the circumferential and axial directions to assess airway anisotropy. Next, samples were subjected to collagenase and elastase enzymatic treatment and tensile tests were repeated. Airway tissue mechanical properties pre- and post-treatment were comprehensively characterized via measures of initial and ultimate moduli, strain transitions, maximum stress, hysteresis, energy loss, and viscoelasticity to gain insights regarding the specialized role of individual connective tissue fibers and network interactions. Results Enzymatic treatment demonstrated an increase in airway tissue compliance throughout loading and resulted in at least a 50% decrease in maximum stress overall. Strain transition values led to significant anisotropic manifestation post-treatment, where circumferential tissues transitioned at higher strains compared to axial counterparts. Hysteresis values and energy loss decreased after enzymatic treatment, where hysteresis reduced by almost half of the untreated value. Anisotropic ratios exhibited axially led stiffness at low strains which transitioned to circumferentially led stiffness when subjected to higher strains. Viscoelastic stress relaxation was found to be greater in the circumferential direction for bronchial airway regions compared to axial counterparts. Conclusion Targeted fiber treatment resulted in mechanical alterations across the loading range and interactions between elastin and collagen connective tissue networks was observed. Providing novel mechanical characterization of elastase and collagenase treated airways aids our understanding of individual and interconnected fiber roles, ultimately helping to establish a foundation for constructing constitutive models to represent various states and progressions of pulmonary disease.

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Section: Introductionmentioning

confidence: 99%

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

et al. 2023

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“…We reproducibly recovered three alternatively-spliced isoforms of elastin, part of the insoluble ECM that is responsible for the expansion capability of the lung (Figure 3F). 37,38 Isoform 1 was identified in both fractions, and isoforms 5 and 11 were recovered exclusively in the Azo fraction. Average sequence coverage for the 8 fibrillar collagens detected was 26.7 ±0.8% and 15.6 ±0.1% for three elastin isoforms (Figure 3G).…”

Section: Resultsmentioning

confidence: 96%

High-throughput Extracellular Matrix Proteomics of Human Lungs Enabled by Photocleavable Surfactant and diaPASEF

Bayne,

Buck,

Towler

et al. 2023

Preprint

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The extracellular matrix (ECM) is a complex assembly of proteins that provide interstitial scaffolding and elastic recoil to human lungs. The pulmonary extracellular matrix (ECM) is increasingly recognized as an independent bioactive entity by creating biochemical and mechanical signals that influence disease pathogenesis, making it an attractive therapeutic target. However, the pulmonary ECM proteome (matrisome) remains challenging to analyze by mass spectrometry due to its inherent biophysical properties and relatively low abundance. Here, we introduce a strategy designed for rapid and efficient characterization of the human pulmonary ECM using the photocleavable surfactant Azo. We coupled this approach with trapped ion mobility MS with diaPASEF to maximize depth of matrisome coverage. Using this strategy, we identify nearly 400 unique matrisome proteins with excellent reproducibility that are known to be important in lung biology, including key insoluble ECM proteins.

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“…Therefore, many studies on the biological repair of aortic aneurysms have focused on the proliferation and functions of these cells. Elastic fibers are important cellular matrix components that are mainly secreted by ECs and SMCs and play a critical role in maintaining the stability of the aortic wall [ 25 ]. During the synthesis of elastic fibers, microfibrils are first synthesized by cells and attached to the cell surface to form a microfibril network for the elastic fibers.…”

Section: Discussionmentioning

confidence: 99%

The synergistic mechanism of fibroblast growth factor 18 and integrin β1 in rat abdominal aortic aneurysm repair

Guo

Ren

et al. 2022

BMC Cardiovasc Disord

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Background Abdominal aortic aneurysms have a high mortality rate. While surgery is the preferred treatment method, the biological repair of abdominal aortic aneurysms is being increasingly studied. We performed cellular and animal experiments to investigate the simultaneous function and mechanism of fibroblast growth factor 18 and integrin β1 in the biological repair of abdominal aortic aneurysms. Methods Endothelial and smooth muscle cells of rat arteries were used for the cellular experiments. Intracellular integrin β1 expression was regulated through lentiviral transfection. Interventions with fibroblast growth factor 18 were determined according to the experimental protocol. Several methods were used to detect the expression of elastic fiber component proteins, cell proliferation, and migratory activity of endothelial and smooth muscle cells after different treatments. For animal experiments, abdominal aortic aneurysms were induced in rats by wrapping the abdominal aortae in sterile cotton balls soaked with CaCl2 solution. Fibroblast growth factor 18 was administered through tail vein injections. The local expression of integrin β1 was regulated through lentiviral injections into the adventitia of the abdominal aortic aneurysms. The abdominal aortae were harvested for pathological examinations and tensile mechanical tests. Results The expression of integrin β1 in endothelial and smooth muscle cells could be regulated effectively through lentiviral transfection. Animal and cellular experiments showed that fibroblast growth factor 18 + integrin β1 could improve the expression of elastic fiber component proteins and enhance the migratory and proliferative activities of smooth muscle and endothelial cells. Moreover, animal experiments showed that fibroblast growth factor 18 + integrin β1 could enhance the aortic integrity to withstand stretch of aortic aneurysm tissue. Conclusion Fibroblast growth factor 18 + integrin β1 improved the biological repair of abdominal aortic aneurysms in rats by increasing the expression of elastic proteins, improving the migratory and proliferative abilities of endothelial and smooth muscle cells, and improving aortic remodeling.

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Elastin in healthy and diseased lung

Cited by 11 publications

References 69 publications

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

High-throughput Extracellular Matrix Proteomics of Human Lungs Enabled by Photocleavable Surfactant and diaPASEF

The synergistic mechanism of fibroblast growth factor 18 and integrin β1 in rat abdominal aortic aneurysm repair

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