scholarly journals Carbamylation of elastic fibers is a molecular substratum of aortic stiffness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manon Doué ◽  
Anaïs Okwieka ◽  
Alexandre Berquand ◽  
Laëtitia Gorisse ◽  
Pascal Maurice ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cardiovascular Diseases ◽  
Aortic Stiffness ◽  
Molecular Mechanisms ◽  
Elastic Fiber ◽  
Plasma Concentrations ◽  
Vascular Wall ◽  
Elastic Fibers ◽  
Fiber Morphology

AbstractBecause of their long lifespan, matrix proteins of the vascular wall, such as elastin, are subjected to molecular aging characterized by non-enzymatic post-translational modifications, like carbamylation which results from the binding of cyanate (mainly derived from the dissociation of urea) to protein amino groups. While several studies have demonstrated a relationship between increased plasma concentrations of carbamylated proteins and the development of cardiovascular diseases, molecular mechanisms explaining the involvement of protein carbamylation in these pathological contexts remain to be fully elucidated. The aim of this work was to determine whether vascular elastic fibers could be carbamylated, and if so, what impact this phenomenon would have on the mechanical properties of the vascular wall. Our experiments showed that vascular elastin was carbamylated in vivo. Fiber morphology was unchanged after in vitro carbamylation, as well as its sensitivity to elastase degradation. In mice fed with cyanate-supplemented water in order to increase protein carbamylation within the aortic wall, an increased stiffness in elastic fibers was evidenced by atomic force microscopy, whereas no fragmentation of elastic fiber was observed. In addition, this increased stiffness was also associated with an increase in aortic pulse wave velocity in ApoE−/− mice. These results provide evidence for the carbamylation of elastic fibers which results in an increase in their stiffness at the molecular level. These alterations of vessel wall mechanical properties may contribute to aortic stiffness, suggesting a new role for carbamylation in cardiovascular diseases.

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.

Mechanical Analysis of Heterogeneous, Atherosclerotic Human Aorta

1998 ◽  
Vol 120 (5) ◽  
pp. 602-607 ◽  
Author(s):  
D. Beattie ◽  
C. Xu ◽  
R. Vito ◽  
S. Glagov ◽  
M. C. Whang
Keyword(s):  
Mechanical Properties ◽  
Cross Sections ◽  
Strain Energy ◽  
Vascular Wall ◽  
Mechanical Analysis ◽  
Human Aorta ◽  
Stress And Strain ◽  
Optimization Strategy

An experimental technique was developed to determine the finite strain field in heterogeneous, diseased human aortic cross sections at physiologic pressures in vitro. Also, the distributions within the cross sections of four histologic features (disease-free zones, lipid accumulations, fibrous intimal tissue, and regions of calcification) were quantified using light microscopic morphometry. A model incorporating heterogeneous, plane stress finite elements coupled the experimental and histologic data. Tissue constituent mechanical properties were determined through an optimization strategy, and the distributions of stress and strain energy in the diseased vascular wall were calculated. Results show that the constituents of atherosclerotic lesions exhibit large differences in their bilinear mechanical properties. The distributions of stress and strain energy in the diseased vascular wall are strongly influenced by both lesion structure and composition. These results suggest that accounting for heterogeneities in the mechanical analysis of atherosclerotic arterial tissue is critical to establishing links between lesion morphology and the susceptibility of plaque to mechanical disruption in vivo.

scholarly journals In Vitro Degradation Behaviours of PDO Monofilament and Its Intravascular Stents with Braided Structure

2016 ◽  
Vol 16 (2) ◽  
pp. 80-89 ◽  
Author(s):  
Cong-er Wang ◽  
Pei-hua Zhang
Keyword(s):  
Mechanical Properties ◽  
Vascular Wall ◽  
Radial Force ◽  
Temporary Increase ◽  
Crystalline Region ◽  
Bending Rigidity ◽  
Intravascular Stents ◽  
Braided Structure ◽  
Intravascular Stent

Abstract Biodegradable intravascular stent has attracted more and more focus in recent years as an effective solution for angiostenosis. Ideal stents were expected to exhibit sufficient radial force to support the vascular wall, while suitable flexibility for the angioplasty. After vascular remodeling, stents should be degraded into small molecular and be eliminated from human body, causing no potential risk. In this paper, poly-p-dioxanone (PDO) monofilament was braided into net structure with four different braiding density, two of which exhibited sufficient radial force larger than 30 kPa, and three of which showed the bending rigidity within 11.7–88.1 N•mm2. The degradation behaviors of monofilaments and stents have been observed for 16 weeks. The findings obtained indicate that degradation first occurred in morphology region, which induced temporary increase of crystallinity, monofilament bending rigidity and stent mechanical properties. During this period, monofilament tends to be hard and brittle and lost its tensile properties. Then the crystalline region was degraded and stent mechanical properties decreased. All the results reveal that the PDO intravascular stents with braided structure were able to afford at least 10 weeks of sufficient support to the vascular wall.

scholarly journals Osteocytes remodel bone by TGF-β-induced YAP/TAZ signaling

2019 ◽  
Author(s):  
Christopher D. Kegelman ◽  
Jennifer C. Coulombe ◽  
Kelsey M. Jordan ◽  
Daniel J. Horan ◽  
Ling Qin ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Bone Matrix ◽  
Protease Gene ◽  
Matrix Remodeling ◽  
Osteoclast Activity ◽  
Control Bone

ABSTRACTOsteocytes are bone matrix-entombed cells that form an interconnected network of processes called the lacunar/canalicular system, which enables osteocytes to coordinate bone formation and resorption. Osteocytes indirectly regulate osteoblast and osteoclast activity on bone surfaces but also directly resorb and deposit their surrounding bone matrix through perilacunar/canalicular remodeling. However, the molecular mechanisms by which osteocytes control bone remodeling remain unclear. We previously reported that the transcriptional regulators Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-motif (TAZ) promote bone acquisition in osteoblast-lineage cells. Here, we tested the hypothesis that YAP and TAZ regulate osteocyte-mediated bone remodeling by conditional ablation of both YAP and TAZ from mouse osteocytes using 8kb-DMP1-Cre. Osteocyte conditional YAP/TAZ deletion reduced bone mass and dysregulated matrix collagen content and organization, which together impaired bone mechanical properties. YAP/TAZ deletion reduced osteoblast number and activity and increased osteoclast activity. In addition, YAP/TAZ deletion directly impaired osteocyte lacunar/canalicular network remodeling, reducing canalicular density, length, and branching, but did not alter lacunar size or shape. Further, consistent with recent studies identifying TGF-β signaling as a key inducer of perilacunar/canalicular remodeling through expression of matrix-remodeling enzymes, YAP/TAZ deletion in vivo decreased osteocyte expression of matrix proteases Mmp13, Mmp14, and Cathepsin K. In vitro, pharmacologic inhibition of YAP/TAZ transcriptional activity in osteocyte-like cells abrogated TGF-β-induced protease gene expression. Together, these data show that YAP and TAZ act downstream of TGF-β in osteocytes to control bone matrix accrual, organization, and mechanical properties indirectly by coordinating osteoblast/osteoclast activity and directly by regulating perilacunar/canalicular remodeling.

scholarly journals Functionally Distinct Tendons From Elastin Haploinsufficient Mice Exhibit Mild Stiffening and Tendon-Specific Structural Alteration

2017 ◽  
Vol 139 (11) ◽  
Author(s):  
Jeremy D. Eekhoff ◽  
Fei Fang ◽  
Lindsey G. Kahan ◽  
Gabriela Espinosa ◽  
Austin J. Cocciolone ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Elastic Fiber ◽  
Mechanical Effect ◽  
Elastic Fibers ◽  
Minor Role ◽  
Tendon Mechanics ◽  
Different Types ◽  
A Minor ◽  
Collagen Alignment

Elastic fibers are present in low quantities in tendon, where they are located both within fascicles near tenocytes and more broadly in the interfascicular matrix (IFM). While elastic fibers have long been known to be significant in the mechanics of elastin-rich tissue (i.e., vasculature, skin, lungs), recent studies have suggested a mechanical role for elastic fibers in tendons that is dependent on specific tendon function. However, the exact contribution of elastin to properties of different types of tendons (e.g., positional, energy-storing) remains unknown. Therefore, this study purposed to evaluate the role of elastin in the mechanical properties and collagen alignment of functionally distinct supraspinatus tendons (SSTs) and Achilles tendons (ATs) from elastin haploinsufficient (HET) and wild type (WT) mice. Despite the significant decrease in elastin in HET tendons, a slight increase in linear stiffness of both tendons was the only significant mechanical effect of elastin haploinsufficiency. Additionally, there were significant changes in collagen nanostructure and subtle alteration to collagen alignment in the AT but not the SST. Hence, elastin may play only a minor role in tendon mechanical properties. Alternatively, larger changes to tendon mechanics may have been mitigated by developmental compensation of HET tendons and/or the role of elastic fibers may be less prominent in smaller mouse tendons compared to the larger bovine and human tendons evaluated in previous studies. Further research will be necessary to fully elucidate the influence of various elastic fiber components on structure–function relationships in functionally distinct tendons.

scholarly journals Acute von Willebrand Factor Secretion from the Endothelium In Vivo: Assessment through Plasma Propeptide (vWf:AgII) Levels

1997 ◽  
Vol 77 (02) ◽  
pp. 387-393 ◽  
Author(s):  
Ulrich M Vischer ◽  
Jørgen Ingerslev ◽  
Claes B Wollheim ◽  
Jean-Claude Mestries ◽  
Dimitrios A Tsakiris ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Time Course ◽  
Plasma Concentrations ◽  
Vascular Wall ◽  
Endothelial Activation ◽  
Relative Increase ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryElevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 µg/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.

Electrospun hybrid nanofibrous meshes with adjustable performance for potential use in soft tissue engineering

2021 ◽  
pp. 004051752110639
Author(s):  
Ye Qi ◽  
Huiyuan Zhai ◽  
Yaning Sun ◽  
Hongxing Xu ◽  
Shaohua Wu ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Tissue Engineering ◽  
Soft Tissue ◽  
Fiber Diameter ◽  
Fiber Morphology ◽  
Surface Hydrophilicity ◽  
Nanofibrous Scaffolds ◽  
Soft Tissue Engineering ◽  
The Mean

Electrospun nanofibrous scaffolds have gained extensive attention in the fields of soft tissue engineering and regenerative medicine. In this study, a series of biodegradable nanofibrous meshes were fabricated by electrospinning poly(ε-caprolactone) (PCL) and poly( p-dioxanone) (PPDO) blends with various mass ratios. All the as-developed PCL/PPDO nanofibrous meshes possessed smooth and highly aligned fiber morphology. The mean fiber diameter was 521.5 ± 76.6 nm for PCL meshes and 485.8 ± 88.9 nm for PPDO meshes, and the mean fiber diameter seemed to present a decreasing tendency with the increasing of the PPDO component. For pure PCL meshes, the contact angle was about 117.5 ± 1.6°, the weight loss ratio was roughly 0.2% after 10 weeks of degradation, and the tensile strength was 41.2 ± 2.3 MPa in the longitudinal direction and 4.2 ± 0.1 MPa in the transverse direction. It was found that the surface hydrophilicity and in vitro degradation properties of PCL/PPDO meshes apparently increased, but the mechanical properties of PCL/PPDO meshes obviously decreased when more PPDO component was introduced. The biological tests showed that 4:1 PCL/PPDO nanofibrous meshes and 1:1 PCL/PPDO nanofibrous meshes could obviously promote the adhesion and proliferation of human adipose derived mesenchymal stem cells more than pure PCL and PPDO meshes and 1:4 PCL/PPDO meshes. The results demonstrated that it is feasible to adjust the surface hydrophilicity, degradation profile, and mechanical properties as well as biological properties of as-obtained nanofibrous meshes by blending PCL and PPDO components. This study provides meaningful reference and guidance for the design and development of PCL/PPDO hybrid nanofibrous scaffolds for soft tissue engineering research and application.

Conventional Nanofat and SVF/ADSC-Concentrated Nanofat: A Comparative Study on Improving Photoaging of Nude Mice Skin

2019 ◽  
Vol 39 (11) ◽  
pp. 1241-1250 ◽  
Author(s):  
Hui Zheng ◽  
Lihong Qiu ◽  
Yingjun Su ◽  
Chenggang Yi
Keyword(s):  
Nude Mice ◽  
Lower Layer ◽  
Elastic Fiber ◽  
Stromal Vascular Fraction ◽  
Collagen Content ◽  
Elastic Fibers ◽  
Saline Injection ◽  
Fiber Morphology ◽  
Dermal Thickness ◽  
Dermal Collagen

AbstractBackgroundNanofats could improve photoaging. Stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) may play pivotal roles. However, SVFs and ADSCs in nanofats processed by conventional methods cannot be enriched. Some researchers have found that after centrifugation, the SVF/ADSC density increases from top to bottom.ObjectivesThe authors hypothesized that centrifugation can be used to obtain SVF/ADSC-concentrated nanofats that are superior to conventional nanofats in improving the photoaging of skin.MethodsAfter a photoaging model was successfully established in nude mice, the back of each mouse was divided into 4 areas and randomly injected with conventional nanofat, centrifuged nanofat (either the middle or lower layer of centrifuged nanofat), or normal saline. Wrinkles, dermis thickness, dermal collagen content, and elastic fiber morphology were measured and compared at weeks 4 and 8.ResultsCompared with the wrinkles in the physiological saline injection areas, the wrinkles in the areas injected with the 3 nanofats (lower and middle layers of centrifuged nanofat and conventional nanofat) were significantly reduced. All 3 nanofat groups showed increased dermal thickness, increased collagen content, and a more regular distribution of elastic fibers compared with the saline injection areas.ConclusionsThe study established the efficacy of nanofats in improving photoaging by reducing wrinkles and increasing the thickness of dermal collagen, making nanofats a promising novel treatment for photoaging. The SVF/ADSC-concentrated nanofats exhibited the most improvement.

scholarly journals Rho Kinase Regulates Aortic Vascular Smooth Muscle Cell Stiffness Via Actin/SRF/Myocardin in Hypertension

2017 ◽  
Vol 44 (2) ◽  
pp. 701-715 ◽  
Author(s):  
Ning Zhou ◽  
Jia-Jye Lee ◽  
Shaunrick Stoll ◽  
Ben Ma ◽  
Kevin D. Costa ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Blood Pressure ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Aortic Stiffness ◽  
Rho Kinase ◽  
Specific Inhibitor ◽  
Wky Rats ◽  
Aortic Stiffening

Background/Aims: Our previous studies demonstrated that intrinsic aortic smooth muscle cell (VSMC) stiffening plays a pivotal role in aortic stiffening in aging and hypertension. However, the underlying molecular mechanisms remain largely unknown. We here hypothesized that Rho kinase (ROCK) acts as a novel mediator that regulates intrinsic VSMC mechanical properties through the serum response factor (SRF) /myocardin pathway and consequently regulates aortic stiffness and blood pressure in hypertension. Methods: Four-month old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were studied. Aortic stiffness was measured by echography. Intrinsic mechanical properties of VSMCs were measured by atomic force microscopy (AFM) in vitro. Results: Compared to WKY rats, SHR showed a significant increase in aortic stiffness and blood pressure, which is accompanied by a remarkable cell stiffening and ROCK activation in thoracic aortic (TA) VSMCs. Theses alterations in SHR were abolished by Y-27632, a specific inhibitor of ROCK. Additionally, boosted filamentous/globular actin ratio was detected in TA VSMCs from SHR versus WKY rats, resulting in an up-regulation of SRF and myocardin expression and its downstream stiffness-associated genes including α-smooth muscle actin, SM22, smoothelin and myosin heavy chain 11. Reciprocally, these alterations in SHR TA VSMCs were also suppressed by Y-27632. Furthermore, a specific inhibitor of SRF/myocardin, CCG-100602, showed a similar effect to Y-27632 in SHR in both TA VSMCs stiffness in vitro and aorta wall stiffness in vivo. Conclusion: ROCK is a novel mediator modulating aortic VSMC stiffness through SRF/myocardin signaling which offers a therapeutic target to reduce aortic stiffening in hypertension.

scholarly journals Nanoindentation of histological specimens: Mapping the elastic properties of soft tissues

2009 ◽  
Vol 24 (3) ◽  
pp. 638-646 ◽  
Author(s):  
R. Akhtar ◽  
N. Schwarzer ◽  
M.J. Sherratt ◽  
R.E.B. Watson ◽  
H.K. Graham ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Elastic Modulus ◽  
Soft Tissues ◽  
Elastic Fiber ◽  
Vena Cava ◽  
Elastic Fibers ◽  
Fiber Density ◽  
Tissue Microstructure ◽  
Micromechanical Properties

Although alterations in the gross mechanical properties of dynamic and compliant tissues have a major impact on human health and morbidity, there are no well-established techniques to characterize the micromechanical properties of tissues such as blood vessels and lungs. We have used nanoindentation to spatially map the micromechanical properties of 5-μm-thick sections of ferret aorta and vena cava and to relate these mechanical properties to the histological distribution of fluorescent elastic fibers. To decouple the effect of the glass substrate on our analysis of the nanoindentation data, we have used the extended Oliver and Pharr method. The elastic modulus of the aorta decreased progressively from 35 MPa in the adventitial (outermost) layer to 8 MPa at the intimal (innermost) layer. In contrast, the vena cava was relatively stiff, with an elastic modulus >30 MPa in both the extracellular matrix-rich adventitial and intimal regions of the vessel. The central, highly cellularized, medial layer of the vena cava, however, had an invariant elastic modulus of ∼20 MPa. In extracellular matrix-rich regions of the tissue, the elastic modulus, as determined by nanoindentation, was inversely correlated with elastic fiber density. Thus, we show it is possible to distinguish and spatially resolve differences in the micromechanical properties of large arteries and veins, which are related to the tissue microstructure.

Sign in / Sign up

Export Citation Format

Share Document