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.

Abstract 13: Inhibition of Nudt6 Stabilizes Advanced Atherosclerotic Plaques

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Hong Jin ◽  
Yuhuang Li ◽  
Ekaterina Chernogubova ◽  
Alexandra Bäcklund ◽  
Stina Sellberg ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Survival Rates ◽  
Atherosclerotic Plaques ◽  
Protein Coding ◽  
Fibrous Cap ◽  
Asymptomatic Patients ◽  
Rupture Model

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.

Human Carotid Atherosclerotic Plaque Growth Function and Progression Simulation Using Meshless GFD and Statistical Methods Based on Multi-Year In Vivo MRI

2008 ◽  
Author(s):  
Chun Yang ◽  
Joseph D. Petruccelli ◽  
Zhongzhao Teng ◽  
Chun Yuan ◽  
Gador Canton ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Wall Thickness ◽  
Vessel Wall ◽  
Plaque Rupture ◽  
Patient Specific ◽  
Tracking Data ◽  
Plaque Progression ◽  
Vessel Wall Thickness ◽  
Plaque Growth

Atherosclerotic plaque rupture and progression have been the focus of intensive investigations in recent years. The mechanisms governing plaque progression and rupture process are not well understood. Using computational models based on patient-specific multi-year in vivo MRI data, our recent results indicated that 18 out of 21 patients studied showed significant negative correlation between plaque progression measured by vessel wall thickness increase (WTI) and plaque wall (structural) stress (PWS) [1]. In this paper, a computational procedure based on meshless generalized finite difference (MGFD) method and serial magnetic resonance imaging (MRI) data was introduced to simulate plaque progression. Participating patients were scanned three times (T1, T2, and T3, at intervals of approximately 18 months) to obtain plaque progression data. Vessel wall thickness (WT) changes were used as the measure for plaque progression. Starting from T2 plaque geometry, plaque progression was simulated by solving the solid model and adjusting wall thickness using plaque growth functions iteratively until time T3 is reached. Numerically simulated plaque progression showed very good agreement with actual plaque geometry at T3 given by MRI data. We believe this is the first time plaque progression simulation results based on multi-year patient-tracking data are reported. Multi-year tracking data and MRI-based progression simulation add time dimension to plaque vulnerability assessment and will improve prediction accuracy.

A Predictive Method for Human Carotid Plaque Rupture Using In Vivo Serial MRI With Follow-Up Scan Showing Actual Rupture and MRI-Based 3D Models With Fluid-Structure Interactions

2011 ◽  
Author(s):  
Zheyang Wu ◽  
Chun Yang ◽  
Dalin Tang
Keyword(s):  
Atherosclerotic Plaque ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
3D Models ◽  
Mechanical Analysis ◽  
Predictive Method ◽  
Magnetic Resonance Imaging Mri ◽  
Serial Mri

It has been hypothesized that mechanical risk factors may be used to predict future atherosclerotic plaque rupture. Much progress has been made in computational modeling, medical imaging, and mechanical analysis for atherosclerotic plaque vulnerability assessment in recent years [1–2]. However, truly predictive methods to predict plaque rupture are currently lacking in the literature and practice. In this paper, we introduce a procedure using computational and statistical models based on serial magnetic resonance imaging (MRI) to quantify sensitivity and specificity of mechanical predictors and their combinations to identify the best candidate for rupture prediction. Serial MRI of carotid plaque from a patient with follow-up scan showing ulceration (rupture) was acquired and the actual appearance of ulceration was used as “gold standard” and validation for the predictive method.

scholarly journals Analysis of MicroRNAs Associated With Carotid Atherosclerotic Plaque Rupture With Thrombosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Nie ◽  
Fan Yang ◽  
Fang Wan ◽  
Shuxuan Jin ◽  
Jun Pu
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Vascular Wall ◽  
Intraplaque Hemorrhage ◽  
Control Group ◽  
Left Carotid Artery ◽  
Mirna Microarray ◽  
Post Surgery ◽  
Atherosclerotic Plaque Rupture

Atherosclerosis is a progressive vascular wall inflammatory disease, and the rupture of atherosclerotic vulnerable plaques is the leading cause of morbidity and mortality worldwide. This study intended to explore the potential mechanisms behind plaque rupture and thrombosis in ApoE knockout mice. The spontaneous plaque rupture models were established, and left carotid artery tissues at different time points (1-, 2-, 4-, 6-, 8-, 12-, and 16-week post-surgery) were collected. By the extent of plaque rupture, plaque was defined as (1) control groups, (2) atherosclerotic plaque group, and (3) plaque rupture group. Macrophage (CD68), MMP-8, and MMP-13 activities were measured by immunofluorescence. Cytokines and inflammatory markers were measured by ELISA. The left carotid artery sample tissue was collected to evaluate the miRNAs expression level by miRNA-microarray. Bioinformatic analyses were conducted at three levels: (2) vs. (1), (3) vs. (2), and again in seven time series analysis. The plaque rupture with thrombus and intraplaque hemorrhage results peaked at 8 weeks and decreased thereafter. Similar trends were seen in the number of plaque macrophages and lipids, the expression of matrix metalloproteinase, and the atherosclerotic and plasma cytokine levels. MiRNA-microarray showed that miR-322-5p and miR-206-3p were specifically upregulated in the atherosclerotic plaque group compared with those in the control group. Meanwhile, miR-466h-5p was specifically upregulated in the plaque rupture group compared with the atherosclerotic plaque group. The highest incidence of plaque rupture and thrombosis occurred at 8 weeks post-surgery. miR-322-5p and miR-206-3p may be associated with the formation of atherosclerotic plaques. miR-466h-5p may promote atherosclerotic plaque rupture via apoptosis-related pathways.

scholarly journals SP-8356, a Novel Inhibitor of CD147-Cyclophilin A Interactions, Reduces Plaque Progression and Stabilizes Vulnerable Plaques in apoE-Deficient Mice

2019 ◽  
Vol 21 (1) ◽  
pp. 95 ◽  
Author(s):  
Kisoo Pahk ◽  
Chanmin Joung ◽  
Hwa Young Song ◽  
Sungeun Kim ◽  
Won-Ki Kim
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Cyclophilin A ◽  
Atherogenic Diet ◽  
Therapeutic Effects ◽  
Plaque Progression ◽  
Artery Ligation ◽  
Apoe Ko Mice ◽  
Apoe Ko

Interactions between CD147 and cyclophilin A (CypA) promote plaque rupture that causes atherosclerosis-related cardiovascular events, such as myocardial infarction and stroke. Here, we investigated whether SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one), a novel drug, can exert therapeutic effects against plaque progression and instability through disruption of CD147-CypA interactions in apolipoprotein E-deficient (ApoE KO) mice. Immunocytochemistry and immunoprecipitation analyses were performed to assess the effects of SP-8356 on CD147-CypA interactions. Advanced plaques were induced in ApoE KO mice via partial ligation of the right carotid artery coupled with an atherogenic diet, and SP-8356 (50 mg/kg) orally administrated daily one day after carotid artery ligation for three weeks. The anti-atherosclerotic effect of SP-8356 was assessed using histological and molecular approaches. SP-8356 interfered with CD147-CypA interactions and attenuated matrix metalloproteinase-9 activation. Moreover, SP-8356 induced a decreased in atherosclerotic plaque size in ApoE KO mice and stabilized plaque vulnerability by reducing the necrotic lipid core, suppressing macrophage infiltration, and enhancing fibrous cap thickness through increasing the content of vascular smooth muscle cells. SP-8356 exerts remarkable anti-atherosclerotic effects by suppressing plaque development and improving plaque stability through inhibiting CD147-CypA interactions. Our novel findings support the potential utility of SP-8356 as a therapeutic agent for atherosclerotic plaque.

Stress Analysis of Carotid Atheroma in Transient Ischemic Attack Patients

2009 ◽  
Author(s):  
Hao Gao ◽  
Quan Long ◽  
Martin Graves ◽  
Jonathan H. Gillard ◽  
Zhi-Yong Li
Keyword(s):  
Magnetic Resonance ◽  
Stress Analysis ◽  
Atherosclerotic Plaque ◽  
Transient Ischemic Attack ◽  
Plaque Rupture ◽  
Magnetic Resonance Images ◽  
Patient Specific ◽  
Critical Information ◽  
Ischemic Attack

Rupture of atherosclerotic plaque is a major cause of mortality. Plaque stress analysis, based on patient-specific multi-sequence in vivo magnetic resonance images (MRI), can provide critical information for the understanding of plaque rupture and could eventually lead to plaque rupture prediction [1].

scholarly journals Hyperelastic modelling of arterial layers with distributed collagen fibre orientations

2005 ◽  
Vol 3 (6) ◽  
pp. 15-35 ◽  
Author(s):  
T. Christian Gasser ◽  
Ray W Ogden ◽  
Gerhard A Holzapfel
Keyword(s):  
Structural Model ◽  
Mechanical Response ◽  
Constitutive Relations ◽  
Polarized Light ◽  
Collagen Fibre ◽  
Middle Layer ◽  
Biological Tissues ◽  
Free Energy Function ◽  
Collagen Fibres ◽  
Small Pitch

Constitutive relations are fundamental to the solution of problems in continuum mechanics, and are required in the study of, for example, mechanically dominated clinical interventions involving soft biological tissues. Structural continuum constitutive models of arterial layers integrate information about the tissue morphology and therefore allow investigation of the interrelation between structure and function in response to mechanical loading. Collagen fibres are key ingredients in the structure of arteries. In the media (the middle layer of the artery wall) they are arranged in two helically distributed families with a small pitch and very little dispersion in their orientation (i.e. they are aligned quite close to the circumferential direction). By contrast, in the adventitial and intimal layers, the orientation of the collagen fibres is dispersed, as shown by polarized light microscopy of stained arterial tissue. As a result, continuum models that do not account for the dispersion are not able to capture accurately the stress–strain response of these layers. The purpose of this paper, therefore, is to develop a structural continuum framework that is able to represent the dispersion of the collagen fibre orientation. This then allows the development of a new hyperelastic free-energy function that is particularly suited for representing the anisotropic elastic properties of adventitial and intimal layers of arterial walls, and is a generalization of the fibre-reinforced structural model introduced by Holzapfel & Gasser (Holzapfel & Gasser 2001 Comput. Meth. Appl. Mech. Eng . 190 , 4379–4403) and Holzapfel et al . (Holzapfel et al . 2000 J. Elast . 61 , 1–48). The model incorporates an additional scalar structure parameter that characterizes the dispersed collagen orientation. An efficient finite element implementation of the model is then presented and numerical examples show that the dispersion of the orientation of collagen fibres in the adventitia of human iliac arteries has a significant effect on their mechanical response.

A platform for high-fidelity patient-specific structural modelling of atherosclerotic arteries: from intravascular imaging to three-dimensional stress distributions

2021 ◽  
Vol 18 (182) ◽  
Author(s):  
Karim Kadry ◽  
Max L. Olender ◽  
David Marlevi ◽  
Elazer R. Edelman ◽  
Farhad R. Nezami
Keyword(s):  
Mechanical Response ◽  
Plaque Rupture ◽  
Three Dimensional ◽  
Computational Modelling ◽  
Material Model ◽  
Patient Specific ◽  
Plaque Morphology ◽  
High Fidelity ◽  
Structural Behaviour ◽  
Heterogeneous Models

The pathophysiology of atherosclerotic lesions, including plaque rupture triggered by mechanical failure of the vessel wall, depends directly on the plaque morphology-modulated mechanical response. The complex interplay between lesion morphology and structural behaviour can be studied with high-fidelity computational modelling. However, construction of three-dimensional (3D) and heterogeneous models is challenging, with most previous work focusing on two-dimensional geometries or on single-material lesion compositions. Addressing these limitations, we here present a semi-automatic computational platform, leveraging clinical optical coherence tomography images to effectively reconstruct a 3D patient-specific multi-material model of atherosclerotic plaques, for which the mechanical response is obtained by structural finite-element simulations. To demonstrate the importance of including multi-material plaque components when recovering the mechanical response, a computational case study was conducted in which systematic variation of the intraplaque lipid and calcium was performed. The study demonstrated that the inclusion of various tissue components greatly affected the lesion mechanical response, illustrating the importance of multi-material formulations. This platform accordingly provides a viable foundation for studying how plaque micro-morphology affects plaque mechanical response, allowing for patient-specific assessments and extension into clinically relevant patient cohorts.

scholarly journals The Hemodynamic Effect of Enhanced External Counterpulsation Treatment on Atherosclerotic Plaque in the Carotid Artery: A Framework of Patient-Specific Computational Fluid Dynamics Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Jianhang Du ◽  
Guangyao Wu ◽  
Bokai Wu ◽  
Chang Liu ◽  
Zhouming Mai ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Carotid Bifurcation ◽  
Patient Specific ◽  
Velocity Spectrum ◽  
External Counterpulsation ◽  
Endothelial Surface ◽  
Computational Fluid Dynamics Analysis ◽  
Enhanced External Counterpulsation

Long-term enhanced external counterpulsation (EECP) therapy has been recommended for antiatherogenesis in recent clinical observations and trials. However, the precise mechanism underlying the benefits has not been fully clarified. To quantify the effect of EECP intervention on arterial hemodynamic environment, a framework of numerical assessment was introduced using a parallel computing algorithm. A 3D endothelial surface of the carotid artery with mild atherosclerotic plaque was constructed from images of magnetic resonance angiography (MRA). Physiologic boundary conditions were derived from images of the ultrasound flow velocity spectrum measured at the common carotid artery and before and during EECP intervention. Hemodynamic factors relating to wall shear stress (WSS) and its spatial and temporal fluctuations were calculated and analyzed, which included AWSS, OSI, and AWSSG. Measuring and computational results showed that diastole blood pressure, perfusion, and WSS level in carotid bifurcation were significantly increased during EECP intervention. Mean AWSS level throughout the model increased by 16.9%, while OSI level did not show a significant change during EECP. We thus suggested that long-term EECP treatment might inhibit the initiation and development of atherosclerotic plaque via improving the hemodynamic environment in the carotid artery. Meanwhile, EECP performance induced a 19.6% increase in AWSSG level, and whether it would influence the endothelial functions may need a further study. Moreover, the numerical method proposed in this study was expected to be useful for the instant assessment of clinical application of EECP .

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