Initial Stress in Biomechanical Models of Atherosclerotic Plaques

Author(s):  
L. Speelman ◽  
A. C. Akyildiz ◽  
J. J. Wentzel ◽  
E. H. van Brummelen ◽  
J. Jukema ◽  
...  

Rupture of the cap of an atherosclerotic plaque is instigated when the stresses in the cap due to the blood pressure exceed the local cap strength. Image based computational finite element models of atherosclerotic plaques are widely used to compute stresses in the fibrous cap. These models are often based on pressurized geometries. The shape of the plaque is determined by the blood pressure at the time of imaging, and thus contains initial stresses (IS) and strains, which are generally ignored in plaque stress studies.

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Hong Jin ◽  
Yuhuang Li ◽  
Ekaterina Chernogubova ◽  
Alexandra Bäcklund ◽  
Stina Sellberg ◽  
...  

Natural antisense transcripts (NATs), a non-coding RNA subclass, being transcribed in antisense direction to protein coding genes, are an intriguing novel class of targetable modulators, exerting crucial effects on gene expression. Aim of the current study was to investigate the contribution of NATs to atherosclerotic plaque vulnerability. Using laser capture micro-dissection, we isolated fibrous caps tissue of carotid artery plaques from 20 symptomatic patients with ruptured lesions vs. 20 samples from asymptomatic patients with stable lesions. A human transcriptome array (HTA; GeneChip 2.0 ) was used to profile the expression of all currently annotated RNA transcripts. Nucleoside diphosphate-linked moiety X motif 6 (NUDT6) was identified as one of the most significantly up-regulated transcripts in fibrous caps of ruptured lesions. Interestingly, NUDT6 is an established antisense RNA targeting the fibroblast growth factor 2 (FGF2). Of importance, FGF2 was among the most significantly down-regulated transcripts in ruptured lesions, corresponding to elevated NUDT6 expression. In situ hybridization in both, human and mouse carotid atherosclerotic plaques, confirmed substantially higher expression levels of NUDT6 in ruptured lesions compared to stable. In addition, in situ hybridization revealed a distinct co-localization with smooth muscle cells (SMCs) in advanced plaques. Overexpression of NUDT6 in cultured human carotid artery SMCs effectively limited FGF2 on the mRNA as well as protein level. Furthermore, reduction of NUDT6 via siRNA stimulated proliferation and blocked apoptosis in SMCs. In an inducible atherosclerotic plaque rupture model using incomplete ligation and cuff placement on common carotid arteries of male apoE -/- mice, NUDT6 inhibition with gapmeRs was able to significantly improve SMC survival rates, leading to thicker fibrous caps, and to reduce the plaque rupture rate compared to scramble-gapmeR control-treated mice (22% vs . 63%, p = 0.03). The present study presents NUDT6 as a novel crucial antisense regulator of fibrous cap stability through steering SMC survival via targeting its sense RNA transcript FGF2.


2019 ◽  
Vol 16 (160) ◽  
pp. 20190430 ◽  
Author(s):  
Elis Newham ◽  
Erika Kague ◽  
Jessye A. Aggleton ◽  
Christianne Fernee ◽  
Kate Robson Brown ◽  
...  

The spine is the central skeletal support structure in vertebrates consisting of repeated units of bone, the vertebrae, separated by intervertebral discs (IVDs) that enable the movement of the spine. Spinal pathologies such as idiopathic back pain, vertebral compression fractures and IVD failure affect millions of people worldwide. Animal models can help us to understand the disease process, and zebrafish are increasingly used as they are highly genetically tractable, their spines are axially loaded like humans, and they show similar pathologies to humans during ageing. However, biomechanical models for the zebrafish are largely lacking. Here, we describe the results of loading intact zebrafish spinal motion segments on a material testing stage within a micro-computed tomography machine. We show that vertebrae and their arches show predictable patterns of deformation prior to their ultimate failure, in a pattern dependent on their position within the segment. We further show using geometric morphometrics which regions of the vertebra deform the most during loading, and that finite-element models of the trunk subjected reflect the real patterns of deformation and strain seen during loading and can therefore be used as a predictive model for biomechanical performance.


1992 ◽  
Vol 45 (6) ◽  
pp. 191-218 ◽  
Author(s):  
Bruce R. Simon

During the last two decades, biological structures with soft tissue components have been modeled using poroelastic or mixture-based constitutive laws, i.e., the material is viewed as a deformable (porous) solid matrix that is saturated by mobile tissue fluid. These structures exhibit a highly nonlinear, history-dependent material behavior; undergo finite strains; and may swell or shrink when tissue ionic concentrations are altered. Given the geometric and material complexity of soft tissue structures and that they are subjected to complicated initial and boundary conditions, finite element models (FEMs) have been very useful for quantitative structural analyses. This paper surveys recent applications of poroelastic and mixture-based theories and the associated FEMs for the study of the biomechanics of soft tissues, and indicates future directions for research in this area. Equivalent finite-strain poroelastic and mixture continuum biomechanical models are presented. Special attention is given to the identification of material properties using a porohyperelastic constitutive law and a total Lagrangian view for the formulation. The associated FEMs are then formulated to include this porohyperelastic material response and finite strains. Extensions of the theory are suggested in order to include inherent viscoelasticity, transport phenomena, and swelling in soft tissue structures. A number of biomechanical research areas are identified, and possible applications of the porohyperelastic and mixture-based FEMs are suggested.


2019 ◽  
Author(s):  
Elis Newman ◽  
Erika Kague ◽  
Jessye A. Aggleton ◽  
Christianne Fernee ◽  
Kate Robson Brown ◽  
...  

AbstractThe spine is the central skeletal support structure in vertebrates consisting of repeated units of bone, the vertebrae, separated by intervertebral discs that enable the movement of the spine. Spinal pathologies such as idiopathic back pain, vertebral compression fractures and intervertebral disc failure affect millions of people world-wide. Animal models can help us to understand the disease process, and zebrafish are increasingly used as they are highly genetically tractable, their spines are axially loaded like humans, and they show similar pathologies to humans during ageing. However biomechanical models for the zebrafish are largely lacking. Here we describe the results of loading intact zebrafish spinal motion segments on a material testing stage within a micro Computed Tomography machine. We show that vertebrae and their arches show predictable patterns of deformation prior to their ultimate failure, in a pattern dependent on their position within the segment. We further show using geometric morphometrics which regions of the vertebra deform the most during loading, and that Finite Element models of the trunk subjected reflect the real patterns of deformation and strain seen during loading and can therefore be used as a predictive model for biomechanical performance.


Author(s):  
Eoghan Maher ◽  
Arthur Creane ◽  
Sherif Sultan ◽  
Niamh Hynes ◽  
Caitríona Lally ◽  
...  

Quantifying the properties of atherosclerotic plaques is critical to improving our understanding of the pathogenesis of the disease. Furthermore realistic tissue properties are vital in order to obtain legitimate results from finite element models of surgical interventions used to treat cardiovascular disease. The aim of this study is to determine the mechanical properties of fresh human carotid plaques immediately following removal during endarterectomy. A number of studies have reported atherosclerotic plaque properties previously [1–3], however all of these tested cadaveric tissue. This study will further investigate in-patient and inter-patient variability, the relationship between plaque properties and their clinical classification (calcified, mixed or echolucent) and the location of the sample (common, internal, external carotid).


2014 ◽  
Vol 493 ◽  
pp. 408-413 ◽  
Author(s):  
Buan Anshari ◽  
Zhong Wei Guan

A new approach to reinforce glulam timber beams has been developed by using compressed wood (CW) which is made of a lower grade wood through densification processes. In the reinforcing practice, compressed wood blocks are inserted into pre-cut holes on the top of glulam beams to produce pre-camber and to generate initial tensile and compressive stresses on the top and the bottom extreme fibre of the glulam beam. In order to optimize the size, the number and the location of CW blocks, 3-D finite element models have been developed. 3D non-linear finite element models have been developed to simulate the pre-camber of Glulam beams locally reinforced by compressed wood blocks. The models developed have also produced the initial tensile and compressive stresses at the top and bottom extreme fibres with building-up moisture-dependent swelling on the CW blocks. With the pre-camber and the initial stress state that cancel out proportions of working deflection and stresses.


2014 ◽  
Vol 11 (93) ◽  
pp. 20131146 ◽  
Author(s):  
Gianni Campoli ◽  
Bart Bolsterlee ◽  
Frans van der Helm ◽  
Harrie Weinans ◽  
Amir A. Zadpoor

Patient-specific biomechanical models including patient-specific finite-element (FE) models are considered potentially important tools for providing personalized healthcare to patients with musculoskeletal diseases. A multi-step procedure is often needed to generate a patient-specific FE model. As all involved steps are associated with certain levels of uncertainty, it is important to study how the uncertainties of individual components propagate to final simulation results. In this study, we considered a specific case of this problem where the uncertainties of the involved steps were known and the aim was to determine the uncertainty of the predicted strain distribution. The effects of uncertainties of three important components of patient-specific models, including bone density, musculoskeletal loads and the parameters of the material mapping relationship on the predicted strain distributions, were studied. It was found that the number of uncertain components and the level of their uncertainty determine the uncertainty of simulation results. The ‘average’ uncertainty values were found to be relatively small even for high levels of uncertainty in the components of the model. The ‘maximum’ uncertainty values were, however, quite high and occurred in the areas of the scapula that are of the greatest clinical relevance. In addition, the uncertainty of the simulation result was found to be dependent on the type of movement analysed, with abduction movements presenting consistently lower uncertainty values than flexion movements.


2011 ◽  
Vol 304 ◽  
pp. 53-58 ◽  
Author(s):  
Fa Rong Gao ◽  
Yun Yuan Gao ◽  
Xu Gang Xi

A blood vessel model of pseudo-elastic constitutive relation in an absolute (vacuum) zero-stress state is employed, and analytical equations of the vessel wall in the three-dimensional stress state are obtained in this paper. The stress distributions in circumferential and axial directions with different blood pressure levels and material parameters are discussed. The results show that the initial stresses of the vessel wall will increase with increment of the blood pressure, the material parameters also affect the distributions of initial stress, in particular, the increase of axial material parameters, will significantly increase axial stress. These methods are importance in the investigation of the vascular dynamic problem, and conclusions are of use in prevention of the related vascular diseases.


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