scholarly journals Studying the Factors of Human Carotid Atherosclerotic Plaque Rupture, by Calculating Stress/Strain in the Plaque, Based on CEUS Images: A Numerical Study

2020 ◽  
Vol 14 ◽  
Author(s):  
Zhenzhou Li ◽  
Yongfeng Wang ◽  
Xinyin Wu ◽  
Xin Liu ◽  
Shanshan Huang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Carotid Artery ◽  
Principal Stress ◽  
Plaque Rupture ◽  
Maximum Principal Stress ◽  
Intraplaque Hemorrhage ◽  
Pulsatile Blood Flow ◽  
Carotid Artery Plaque ◽  
Fibrous Cap ◽  
Luminal Stenosis

Carotid plaque neovascularization is one of the major factors for the classification of vulnerable plaque, but the axial force effects of the pulsatile blood flow on the plaque with neovessel and intraplaque hemorrhage was unclear. Together with the severity of stenosis, the fibrous cap thickness, large lipid core, and the neovascularization followed by intraplaque hemorrhage (IPH) have been regarded as high-risk features of plaque rupture. In this work, the effects of these factors were evaluated on the progression and rupture of the carotid atherosclerotic plaques. Five geometries of carotid artery plaque were developed based on contrast-enhanced ultrasound (CEUS) images, which contain two types of neovessel and IPH, and geometry without neovessel and IPH. A one-way fluid-structure interaction model was applied to compute the maximum principal stress and strain in the plaque. For that hyper-elastic and non-linear material, Yeoh 3rd Order strain energy density function was used for components of the plaque. The simulation results indicated that the maximum principal stress of plaque in the carotid artery was higher when the degree of the luminal stenosis increased and the thickness of the fibrous cap decreased. The neovessels within the plaque could introduce a 2.5% increments of deformation in the plaque under the pulsatile blood flow pressure. The IPH also contributed to the increased risk of plaque rupture that a gain of stress was 8.983, 14.526, and 34.47 kPa for the plaque with 50, 65, and 75%, respectively, when comparing stress in the plaque with IPH distributed at the middle to the shoulder of the plaque. In conclusion, neovascularization in the plaque could reduce the stability of the plaque by increasing the stress within the plaque. Also, the risk of plaque rupture increased when large luminal stenosis, thin fibrous cap, and IPH were observed.

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.

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 Reduction of TMAO level enhances the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis

2021 ◽  
Author(s):  
Weihao Shi ◽  
Yijun Huang ◽  
Zhou Yang ◽  
Liang Zhu ◽  
Bo Yu
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Raw264.7 Cells ◽  
Carotid Atherosclerotic Plaque ◽  
Obvious Effect ◽  
Carotid Artery Plaque ◽  
Fibrous Cap ◽  
M2 Polarization ◽  
Significant Difference ◽  
The Stability

It has been demonstrated that trimethylamine N-oxide (TMAO) serves as a driver of atherosclerosis, suggesting that reduction of TMAO level might be a potent method to prevent the progression of atherosclerosis. Herein, we explored the role of TMAO in the stability of carotid atherosclerotic plaques, and disclosed the underlying mechanisms. The unstable carotid artery plaque models were established in C57/BL6 mice. L-carnitine (LCA) and methimazole (MMI) administration were applied to increase and reduce TMAO levels. Hematoxylin and eosin (H&E) staining, Sirius red , Perl’s staining, Masson trichrome staining and immunohistochemical staining with CD68 staining were used to for histopathology analysis of the carotid artery plaque. M1 and M2 macrophagocyte markers were assessed by RT-PCR to determine the polarization of RAW264.7 cells. MMI administration for 2 weeks significantly decreased the plaque area, increased the thickness of the fibrous cap and reduced the size of the necrotic lipid cores, whereas 5-week of administration of MMI induced intraplate hemorrhage. LCA treatment further deteriorated the carotid atherosclerotic plaque, but with no significant difference. In mechanism, we found that TMAO treatment impaired the M2 polarization and efferocytosis of RAW264.7 cells, with no obvious effect on the M1 polarization. In conclusion, this study demonstrated that TMAO reduction enhanced the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.

Stress Concentrations of Vulnerable Plaques With a Composite Variable Core

2010 ◽  
Author(s):  
Eyass Massarwa ◽  
Aronis Ze’ev ◽  
Rami Eliasy ◽  
Rami Haj-Ali ◽  
Shmuel Einav
Keyword(s):  
Plaque Rupture ◽  
Necrotic Core ◽  
Intraplaque Hemorrhage ◽  
Plaque Morphology ◽  
Rapid Progression ◽  
Stress Concentrations ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Vulnerable Plaques ◽  
Life Threatening

Vulnerable plaques are inflamed, active, and growing lesions which are prone to complications such as rupture, luminal and mural thrombosis, intraplaque hemorrhage, and rapid progression to stenosis. It remains difficult to assess what factors influence the biomechanical stability of vulnerable plaques and promote some of them to rupture while others remain intact. The rupture of thin fibrous cap overlying the necrotic core of a vulnerable plaque is the principal cause of acute coronary syndrome. The mechanism or mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to a life threatening athero-thrombotic lesion are not fully understood. It has been widely assumed that plaque morphology is the major determinant of clinical outcome [1, 2]. Thin-cap fibroatheroma with a large necrotic core and a fibrous cap of < 65μm was describes as a more specific precursor of plaque rupture due to tissue stress.

scholarly journals Computational Investigation of the Stability of Stenotic Carotid Artery under Pulsatile Blood Flow Using a Fluid-Structure Interaction Approach

2020 ◽  
pp. 2050110
Author(s):  
Amirhosein Manzoori ◽  
Famida Fallah ◽  
Mohammadali Sharzehee ◽  
Sina Ebrahimi
Keyword(s):  
Blood Flow ◽  
Carotid Artery ◽  
Fluid Structure Interaction ◽  
Circumferential Stress ◽  
Artery Stenosis ◽  
Shear Stresses ◽  
Pulsatile Blood Flow ◽  
Fluid Structure ◽  
Structure Interaction ◽  
The Stability

Stenosis can disrupt the normal pattern of blood flow and make the artery more susceptible to buckling which may cause arterial tortuosity. Although the stability simulations of the atherosclerotic arteries were conducted based on solid modeling and static internal pressure, the mechanical stability of stenotic artery under pulsatile blood flow remains unclear while pulsatile nature of blood flow makes the artery more critical for stresses and stability. In this study, the effect of stenosis on arterial stability under pulsatile blood flow was investigated. Fluid–structure interaction (FSI) simulations of artery stenosis under pulsatile flow were conducted. 3D idealized geometries of carotid artery stenosis with symmetric and asymmetric plaques along with different percentages of stenosis were created. It was observed that the stenosis percentage, symmetry/asymmetry of the plaque, and the stretch ratio can dramatically affect the buckling pressure. Buckling makes the plaques (especially in asymmetric ones) more likely to rupture due to increasing the stresses on it. The dominant stresses on plaques are the circumferential, axial and radial ones, respectively. Also, the highest shear stresses on the plaques were detected in [Formula: see text] and [Formula: see text] planes for the symmetric and asymmetric stenotic arteries, respectively. In addition, the maximum circumferential stress on the plaques was observed in the outer point of the buckled configuration for symmetric and asymmetric stenosis as well as at the ends of the asymmetric plaque. Furthermore, the artery buckling causes a large vortex flow at the downstream of the plaque. As a result, the conditions for the penetration of lipid particles and the formation of new plaques are provided.

Carotid Artery Plaque Calcifications: Lessons From Histopathology to Diagnostic Imaging

Stroke ◽  
2021 ◽  
Author(s):  
Luca Saba ◽  
Valentina Nardi ◽  
Riccardo Cau ◽  
Ajay Gupta ◽  
Hooman Kamel ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Plaque ◽  
Intraplaque Hemorrhage ◽  
Calcium Deposition ◽  
Carotid Artery Plaque ◽  
Carotid Plaques ◽  
Novel Technologies ◽  
Carotid Artery Calcification ◽  
Wide Range

The role of calcium in atherosclerosis is controversial and the relationship between vascular calcification and plaque vulnerability is not fully understood. Although calcifications are present in ≈50% to 60% of carotid plaques, their association with cerebrovascular ischemic events remains unclear. In this review, we summarize current understanding of carotid plaque calcification. We outline the role of calcium in atherosclerotic carotid disease by analyzing laboratory studies and histopathologic studies, as well as imaging findings to understand clinical implications of carotid artery calcifications. Differences in mechanism of calcium deposition express themselves into a wide range of calcification phenotypes in carotid plaques. Some patterns, such as rim calcification, are suggestive of plaques with inflammatory activity with leakage of the vasa vasourm and intraplaque hemorrhage. Other patterns such as dense, nodular calcifications may confer greater mechanical stability to the plaque and reduce the risk of embolization for a given degree of plaque size and luminal stenosis. Various distributions and patterns of carotid plaque calcification, often influenced by the underlying systemic pathological condition, have a different role in affecting plaque stability. Modern imaging techniques afford multiple approaches to assess geometry, pattern of distribution, size, and composition of carotid artery calcifications. Future investigations with these novel technologies will further improve our understanding of carotid artery calcification and will play an important role in understanding and minimizing stroke risk in patients with carotid plaques.

Intraplaque Hemorrhage, Fibrous Cap Status, and Microembolic Signals in Symptomatic Patients With Mild to Moderate Carotid Artery Stenosis

Stroke ◽  
2014 ◽  
Vol 45 (11) ◽  
pp. 3423-3426 ◽  
Author(s):  
Martine T.B. Truijman ◽  
Alexandra A.J. de Rotte ◽  
Rune Aaslid ◽  
Anouk C. van Dijk ◽  
Jeire Steinbuch ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Artery Stenosis ◽  
Intraplaque Hemorrhage ◽  
Fibrous Cap
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