scholarly journals Microstructural Characterization of Resistance Artery Remodelling in Diabetes Mellitus

2021 ◽  
pp. 1-11
Author(s):  
James S. Bell ◽  
Aminat O. Adio ◽  
Andrew Pitt ◽  
Lindsay Hayman ◽  
Clare E. Thorn ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Second Harmonic ◽  
Collagen Fibre ◽  
Local Stress ◽  
Microstructural Characterization ◽  
Outer Wall ◽  
Resistance Arteries ◽  
Internal Elastic Lamina ◽  
Mechanical Environment ◽  
Wall Area

<b><i>Introduction:</i></b> Microvascular remodelling is a symptom of cardiovascular disease. Despite the mechanical environment being recognized as a major contributor to the remodelling process, it is currently only understood in a rudimentary way. <b><i>Objective:</i></b> A morphological and mechanical evaluation of the resistance vasculature in health and diabetes mellitus. <b><i>Methods:</i></b> The cells and extracellular matrix of human subcutaneous resistance arteries from abdominal fat biopsies were imaged using two-photon fluorescence and second harmonic generation at varying transmural pressure. The results informed a two-layer mechanical model. <b><i>Results:</i></b> Diabetic resistance arteries reduced in wall area as pressure was increased. This was attributed to the presence of thick, straight collagen fibre bundles that braced the outer wall. The abnormal mechanical environment caused the internal elastic lamina and endothelial and vascular smooth muscle cell arrangements to twist. <b><i>Conclusions:</i></b> Our results suggest diabetic microvascular remodelling is likely to be stress-driven, comprising at least 2 stages: (1) Laying down of adventitial bracing fibres that limit outward distension, and (2) Deposition of additional collagen in the media, likely due to the significantly altered mechanical environment. This work represents a step towards elucidating the local stress environment of cells, which is crucial to build accurate models of mechanotransduction in disease.

scholarly journals The Influence of Bulb Position on Hydraulic Performance of Submersible Tubular Pump Device

2021 ◽  
Vol 9 (8) ◽  
pp. 831
Author(s):  
Zhuangzhuang Sun ◽  
Jie Yu ◽  
Fangping Tang
Keyword(s):  
Entropy Production ◽  
Large Scale ◽  
Experimental Testing ◽  
Guide Vane ◽  
Outer Wall ◽  
Hydraulic Performance ◽  
Hydraulic Loss ◽  
Optimized Design ◽  
Outlet Channel ◽  
Wall Area

In order to study the influence of the position of the bulb on the hydraulic performance of asubmersible tubular pump device, based on a large-scale pumping station, two schemes—involving a front-mounted bulb and a rear-mounted bulb, respectively—were designed. The front-mounted scheme uses the GL-2008-03 hydraulic model and its conventional guide vane, while the rearmounted scheme uses the optimized design of a diffuser vane. The method of combining numerical simulation and experimental testing was used to analyze the differences between the external and internal characteristics of the two schemes. The results show that, under the condition of reasonable diffusion guide vane design, the efficiency under the rear-mounted scheme is higher than that under the front-mounted scheme, where the highest efficiency difference is about 1%. Although the frontmounted bulb scheme reduces the hydraulic loss of the bulb section, the placement of the bulb on the water inlet side reduces the flow conditions of the impeller. Affected by the circulation of the guide vane outlet, the hydraulic loss of the outlet channel is greater than the rear-mounted scheme. The bulb plays a rectifying function when the bulb is placed behind, which greatly eliminates the annular volume of the guide vane outlet, and the water outlet channel has a smaller hydraulic loss. In the front-mounted scheme, the water flow inside the outlet channel squeezes to the outer wall, causing higher entropy production near the outer wall area. The entropy production of the rear-mounted scheme is mainly in the bulb section and the bulb support. This research can provide reference for the design and form selection of a submersible tubular pump device, which has great engineering significance.

scholarly journals Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition

2021 ◽  
Vol 14 (3) ◽  
pp. dmm048116 ◽  
Author(s):  
Aikta Sharma ◽  
Alice Goring ◽  
Peter B. Johnson ◽  
Roger J. H. Emery ◽  
Eric Hesse ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Ex Vivo ◽  
Second Harmonic ◽  
Collagen Fibre ◽  
Matrix Composition ◽  
Label Free ◽  
Fibre Number ◽  
Backscattered Electron ◽  
Matrix Mineralisation

ABSTRACTCollagen assembly during development is essential for successful matrix mineralisation, which determines bone quality and mechanocompetence. However, the biochemical and structural perturbations that drive pathological skeletal collagen configuration remain unclear. Deletion of vascular endothelial growth factor (VEGF; also known as VEGFA) in bone-forming osteoblasts (OBs) induces sex-specific alterations in extracellular matrix (ECM) conformation and mineralisation coupled to vascular changes, which are augmented in males. Whether this phenotypic dimorphism arises as a result of the divergent control of ECM composition and its subsequent arrangement is unknown and is the focus of this study. Herein, we used murine osteocalcin-specific Vegf knockout (OcnVEGFKO) and performed ex vivo multiscale analysis at the tibiofibular junction of both sexes. Label-free and non-destructive polarisation-resolved second-harmonic generation (p-SHG) microscopy revealed a reduction in collagen fibre number in males following the loss of VEGF, complemented by observable defects in matrix organisation by backscattered electron scanning electron microscopy. This was accompanied by localised divergence in collagen orientation, determined by p-SHG anisotropy measurements, as a result of OcnVEGFKO. Raman spectroscopy confirmed that the effect on collagen was linked to molecular dimorphic VEGF effects on collagen-specific proline and hydroxyproline, and collagen intra-strand stability, in addition to matrix carbonation and mineralisation. Vegf deletion in male and female murine OB cultures in vitro further highlighted divergence in genes regulating local ECM structure, including Adamts2, Spp1, Mmp9 and Lama1. Our results demonstrate the utility of macromolecular imaging and spectroscopic modalities for the detection of collagen arrangement and ECM composition in pathological bone. Linking the sex-specific genetic regulators to matrix signatures could be important for treatment of dimorphic bone disorders that clinically manifest in pathological nano- and macro-level disorganisation.This article has an associated First Person interview with the first author of the paper.

Abstract 3736: Applying the Carotid Atherosclerosis Score in a Clinical Environment: a Feasibility Study

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Dongxiang Xu ◽  
Jie Sun ◽  
Yan Song ◽  
Daniel S Hippe ◽  
Min Chen ◽  
...  
Keyword(s):  
Neurological Symptom ◽  
Carotid Atherosclerosis ◽  
Treatment Options ◽  
Outer Wall ◽  
Classification Performance ◽  
Clinical Environment ◽  
Plaque Instability ◽  
Wall Area ◽  
Increasing Trend ◽  
Symptom Status

Background Carotid atherosclerosis is a leading cause of stoke. Recent studies have shown that its severity can be stratified by the Carotid Atherosclerosis Score (CAS) as measured by MRI. However, these studies were performed using customized imaging sequences, coils and comprehensive plaque analysis by specialized human reviewers, which are not generally available in a clinical environment. Whether CAS can be applied for clinical risk assessment is unknown. In this study, we used clinically collected MRI data to compute CAS. We investigated the correlation between CAS and the prevalence of neurological symptoms and disrupted luminal surface (DLS), an indicator of plaque instability, to evaluate the feasibility of translating CAS for clinical use. Methods Seventy six patients with either symptomatic or asymptomatic carotid disease detected by ultrasound were recruited. All patients underwent a multi-contrast MRI with clinical sequences and a commercially available coil. The lumen and outer wall boundaries and DLS were outlined manually and the plaque components were identified automatically using histologically validated image analysis software. The maximum wall thickness (MWT) and maximum % area (100 x area/[wall area]) of lipid-rich necrotic core (LRNC) were outputted by the software to compute CAS as follows: CAS=1 with MWT&lt2.0mm, CAS=2 with LRNC&lt20%, CAS=3 with LRNC between 20% and 40% and CAS=4 with LRNC&gt40%. Trend analysis was done to evaluate the associations between CAS and prevalence of symptoms and DLS. The area under the receiver operating characteristic (ROC) curve was used to evaluate the classification performance of CAS. Results Of the 76 patients, there was a significant increasing trend (p=0.01) between CAS scores and neurological symptom status. The presence of DLS also demonstrated a significant increasing trend (p&lt0.001) versus CAS with rates 0% (0/7), 7% (2/27), 35% (7/20) and 59% (13/22). ROC analysis of CAS also showed it was a good classifier of symptom status (AUC = 0.67, p=0.01) and DLS (AUC = 0.80, p&lt0.001) Conclusion In this study, we conclude that the CAS computed from clinically collected MRI data can stratify the severity of carotid atherosclerotic disease as indicated by neurological symptom status and DLS, both of which are important in monitoring patients and evaluating treatment options. Further study is needed to assess how a fully automated CAS analysis affects the quality of the score and how well the score can stratify the risk of future outcomes.

scholarly journals Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries

2017 ◽  
Vol 313 (1) ◽  
pp. H164-H178 ◽  
Author(s):  
Maria Bloksgaard ◽  
Thomas M. Leurgans ◽  
Bart Spronck ◽  
Maarten H. G. Heusinkveld ◽  
Bjarne Thorsted ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Extracellular Matrix ◽  
Quantitative Relationship ◽  
Model System ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Internal Elastic Lamina ◽  
Integrated Method ◽  
Induced Changes ◽  
The Impact

The impact of disease-related changes in the extracellular matrix (ECM) on the mechanical properties of human resistance arteries largely remains to be established. Resistance arteries from both pig and human parietal pericardium (PRA) display a different ECM microarchitecture compared with frequently used rodent mesenteric arteries. We hypothesized that the biaxial mechanics of PRA mirror pressure-induced changes in the ECM microarchitecture. This was tested using isolated pig PRA as a model system, integrating vital imaging, pressure myography, and mathematical modeling. Collagenase and elastase digestions were applied to evaluate the load-bearing roles of collagen and elastin, respectively. The incremental elastic modulus linearly related to the straightness of adventitial collagen fibers circumferentially and longitudinally (both R2 ≥ 0.99), whereas there was a nonlinear relationship to the internal elastic lamina elastin fiber branching angles. Mathematical modeling suggested a collagen recruitment strain (means ± SE) of 1.1 ± 0.2 circumferentially and 0.20 ± 0.01 longitudinally, corresponding to a pressure of ~40 mmHg, a finding supported by the vital imaging. The integrated method was tested on human PRA to confirm its validity. These showed limited circumferential distensibility and elongation and a collagen recruitment strain of 0.8 ± 0.1 circumferentially and 0.06 ± 0.02 longitudinally, reached at a distending pressure below 20 mmHg. This was confirmed by vital imaging showing negligible microarchitectural changes of elastin and collagen upon pressurization. In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies. NEW & NOTEWORTHY This is the first study to quantitatively relate pressure-induced microstructural changes in resistance arteries to the mechanics of their wall. Principal findings using a pig model system were confirmed in human arteries. The combined methods provide a strong tool for future hypothesis-driven studies of microvascular pathologies.

scholarly journals Development of a Collagen Fibre Remodelling Rupture Risk Metric for Potentially Vulnerable Carotid Artery Atherosclerotic Plaques

2021 ◽  
Vol 12 ◽  
Author(s):  
Milad Ghasemi ◽  
Robert D. Johnston ◽  
Caitríona Lally
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Mechanical Response ◽  
Plaque Rupture ◽  
Collagen Fibre ◽  
Local Stress ◽  
Patient Specific ◽  
Collagen Fibres ◽  
Magnetic Resonance Imaging Mri ◽  
Risk Metric

Atherosclerotic plaque rupture in carotid arteries can lead to stroke which is one of the leading causes of death or disability worldwide. The accumulation of atherosclerotic plaque in an artery changes the mechanical properties of the vessel. Whilst healthy arteries can continuously adapt to mechanical loads by remodelling their internal structure, particularly the load-bearing collagen fibres, diseased vessels may have limited remodelling capabilities. In this study, a local stress modulated remodelling algorithm is proposed to explore the mechanical response of arterial tissue to the remodelling of collagen fibres. This stress driven remodelling algorithm is used to predict the optimum distribution of fibres in healthy and diseased human carotid bifurcations obtained using Magnetic Resonance Imaging (MRI). In the models, healthy geometries were segmented into two layers: media and adventitia and diseased into four components: adventitia, media, plaque atheroma and lipid pool (when present in the MRI images). A novel meshing technique for hexahedral meshing of these geometries is also demonstrated. Using the remodelling algorithm, the optimum fibre patterns in various patient specific plaques are identified and the role that deviations from these fibre configurations in plaque vulnerability is shown. This study provides critical insights into the collagen fibre patterns required in carotid artery and plaque tissue to maintain plaque stability.

scholarly journals Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo

2016 ◽  
Vol 310 (9) ◽  
pp. H1091-H1096 ◽  
Author(s):  
Erika M. Boerman ◽  
Jesse E. Everhart ◽  
Steven S. Segal
Keyword(s):  
Calcium Signaling ◽  
Fluorescent Protein ◽  
Vascular Dysfunction ◽  
Tissue Perfusion ◽  
Mesenteric Arteries ◽  
Advanced Age ◽  
Resistance Arteries ◽  
Internal Elastic Lamina ◽  
Effects Of Aging

Aging is associated with vascular dysfunction that impairs tissue perfusion, physical activity, and the quality of life. Calcium signaling in endothelial cells (ECs) is integral to vasomotor control, exemplified by localized Ca2+ signals within EC projections through holes in the internal elastic lamina (IEL). Within these microdomains, endothelium-derived hyperpolarization is integral to smooth muscle cell (SMC) relaxation via coupling through myoendothelial gap junctions. However, the effects of aging on local EC Ca2+ signals (and thereby signaling between ECs and SMCs) remain unclear, and these events have not been investigated in vivo. Furthermore, it is unknown whether aging affects either the number or the size of IEL holes. In the present study, we tested the hypothesis that local EC Ca2+ signaling is impaired with advanced age along with a reduction in IEL holes. In anesthetized mice expressing a Ca2+-sensitive fluorescent protein (GCaMP2) selectively in ECs, our findings illustrate that for mesenteric arteries controlling splanchnic blood flow the frequency of spontaneous local Ca2+ signals in ECs was reduced by ∼85% in old (24–26 mo) vs. young (3–6 mo) animals. At the same time, the number (and total area) of holes per square millimeter of IEL was reduced by ∼40%. We suggest that diminished signaling between ECs and SMCs contributes to dysfunction of resistance arteries with advanced age. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-impairs-endothelial-ca2-signaling/ .

scholarly journals Increasing Value of Façade at Green Hotel Building Based on Value Engineering

2021 ◽  
Vol 15 (1) ◽  
pp. 398-405
Author(s):  
Albert Eddy Husin ◽  
Tenni Karolina ◽  
Diah Ika Rahmawati ◽  
Chandra Fany Abdillah
Keyword(s):  
Environmental Sustainability ◽  
Green Building ◽  
Electrical Energy ◽  
Outer Wall ◽  
Value Engineering ◽  
Energy Sources ◽  
Wall Area ◽  
High Rise ◽  
Green Hotel ◽  
Nature Preservation

Background: Of a total of 180 countries in the world, Indonesia is ranked 116th in the EPI ranking. This paper describes the innovative design of a high-rise hotel building that carries a green building concept. which utilizes the outer wall area of the hotel building as an object in this study. Objective: The main design of this project is the creation of an innovative high-rise hotel building with attention to architectural, structural, and lighting system aspects as well as energy efficiency from direct sunlight, which will be processed into a source of electrical energy. Materials and Methods: Application of analysis through value engineering case studies and application of green building methods, with qualitative methods. This paper focuses on factors related to energy sources and environmental sustainability and calculates life cycle costs concerning case study designs. The goal is to reduce the use of electrical energy sources from PLN which have an impact on nature preservation, by carrying out the concept of environmentally friendly buildings, by utilizing the facade wall area with the application of Photovoltaic. Results: The results obtained a percentage of ≤ 6.21%, with the use of Photovoltaic material as much as 100%. Conclusion: The facades (east and west) generate ± 1,050 KVA of electricity from the Solar Power Plant and reduce the use of electricity from PLN by 991 KVA, out of a total of 2,041 KVA. It can be concluded that the decrease obtained is 47.32%.

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