scholarly journals Mathematical modeling of intraplaque neovascularization and hemorrhage in a carotid atherosclerotic plaque

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Cai ◽  
Jichao Pan ◽  
Zhiyong Li
Keyword(s):  
Atherosclerotic Plaque ◽  
Carotid Plaque ◽  
Reaction Diffusion Equations ◽  
Vasa Vasorum ◽  
Intraplaque Hemorrhage ◽  
Model Parameters ◽  
Interstitial Tissue ◽  
Plaque Progression ◽  
Imaging Data ◽  
Density Region

Abstract Background Growing experimental evidence has identified neovascularization from the adventitial vasa vasorum and induced intraplaque hemorrhage (IPH) as critical indicators during the development of vulnerable atherosclerotic plaques. In this study, we propose a mathematical model incorporating intraplaque angiogenesis and hemodynamic calculation of the microcirculation, to obtain the quantitative evaluation of the influences of intraplaque neovascularization and hemorrhage on vulnerable plaque development. A two-dimensional nine-point model of angiogenic microvasculature is generated based on the histology of a patient’s carotid plaque. The intraplaque angiogenesis model includes three key cells (endothelial cells, smooth muscle cells, and macrophages) and three key chemical factors (vascular endothelial growth factors, extracellular matrix, and matrix metalloproteinase), which densities and concentrations are described by a series of reaction–diffusion equations. The hemodynamic calculation by coupling the intravascular blood flow, the extravascular plasma flow, and the transvascular transport is carried out on the generated angiogenic microvessel network. We then define the IPH area by using the plasma concentration in the interstitial tissue, as well as the extravascular transport across the capillary wall. Results The simulational results reproduce a series of pathophysiological phenomena during the atherosclerotic plaque progression. It is found that the high microvessel density region at the shoulder areas and the extravascular flow across the leaky wall of the neovasculature contribute to the IPH observed widely in vulnerable plaques. The simulational results are validated by both the in vivo MR imaging data and in vitro experimental observations and show significant consistency in quantity ground. Moreover, the sensitivity analysis of model parameters reveals that the IPH area and extent can be reduced significantly by decreasing the MVD and the wall permeability of the neovasculature. Conclusions The current quantitative model could help us to better understand the roles of microvascular and intraplaque hemorrhage during the carotid plaque progression.

scholarly journals Mathematical Modeling of Intraplaque Neovascularization and Hemorrhage in a Carotid Atherosclerotic Plaque

2021 ◽  
Author(s):  
Y Cai ◽  
Jichao Pan ◽  
Zhiyong Li
Keyword(s):  
Atherosclerotic Plaque ◽  
Plasma Flow ◽  
Carotid Plaque ◽  
Reaction Diffusion Equations ◽  
Vasa Vasorum ◽  
Intraplaque Hemorrhage ◽  
Model Parameters ◽  
Interstitial Tissue ◽  
Plaque Progression ◽  
Imaging Data

Abstract Background Growing experimental evidence has identified neovascularization from the adventitial vasa vasorum and induced intraplaque hemorrhage (IPH) as critical indicators during the development of vulnerable atherosclerotic plaques. In this study, we propose a mathematical model incorporating intraplaque angiogenesis and hemodynamic calculation of the microcirculation, in order to obtain the quantitative evaluation of the influences of intraplaque neovascularization and hemorrhage on the vulnerable plaque development. A two-dimensional nine-point model of angiogenic microvasculature is generated based on histology of a patient’s carotid plaque. The intraplaque angiogenesis model includes three key cells (endothelial cells, smooth muscle cells and macrophages) and three key chemical factors (vascular endothelial growth factors, extracellular matrix and matrix metalloproteinase), which densities and concentrations are described by a series of reaction-diffusion equations. The hemodynamic calculation by coupling the intravascular blood flow, the extravascular plasma flow and the transvascular transport is carried out on the generated angiogenic microvessel network. We then define the IPH area by using the plasma concentration in the interstitial tissue, as well as the extravascular transport across the capillary wall. Results The simulational results reproduce a series of pathophysiological phenomena during the atherosclerotic plaque progression, such as the high microvessel density region at the shoulder areas, the enlarged necrotic core, and the IPH caused by the extravascular plasma flow across the leaky wall of the neovasculature. The simulational results show significant consistency with both the MR imaging data and in vitro experimental observations in quantity ground. Moreover, the sensitivity analysis of model parameters reveals that the IPH area and extent can be reduced significantly by decreasing the MVD and the wall permeability of the neovasculature. Conclusions The current quantitative model could help us to better understand the roles of microvascular and intraplaque hemorrhage during the carotid plaque progression.

Abstract 1143: Imaging of Vasa Vasorum in Atherosclerotic Plaque with 99m Tc-labeled single chain-VEGF

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoru Ohshima ◽  
Shinichiro Fujimoto ◽  
Sotirios Tsimikas ◽  
Frank D Kolodgie ◽  
Renu Virmani ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Atherosclerotic Lesion ◽  
Vasa Vasorum ◽  
Intraplaque Hemorrhage ◽  
Control Group ◽  
High Cholesterol Diet ◽  
Single Chain

Introduction: Adventitial vasa vasorum proliferation and neointimal neovascularization are associated with intraplaque hemorrhage, expansion of necrotic core and hence plaque vulnerability. Increased expression of VEGF and its receptors accompany neoangiogenic process. We used 99m Tc -labeled single chain VEGF (TcV) for developing potentially noninvasive imaging modality in experimentally induced aortic atherosclerotic lesion. Methods : Noninva-sive radionuclide imaging was performed with TcV (6.85 ±0. 27 mCi) in 6 NZW rabbits receiving high cholesterol diet (0.2% cholesterol, 4% fat) for one year and compared with 3 control rabbits receiving normal rabbit chow. Four hours after intravenous administration of TcV, micro SPECT/microCT imaging was performed for in vivo localization of tracer activity. Aortas were then explanted, and gamma counted for determination of % injected dose per gram (%ID/g). The aortas were then submitted for histopathologic characterization. Results : The uptake in thoracic aorta was clearly visualized non-invasively by TcV in vivo imaging in 4 of 5 rabbits in hypercholesterolemic rabbits, but not in the control animals. The %ID/g of each parts of aorta in hypercholesterolemic rabbits (Arch : 0.036 ± 0.020 %, Thoracic : 0.026 ± 0.012 %, Abd : 0.019 ± 0.009 %) was about 2.5-fold higher than that in control group (Arch : 0.014 ± 0.004 %, Thoracic : 0.009 ± 0.003 %, Abd : 0.009 ± 0.003 %) (figure a ). Ex vivo images of each group are shown as figure b . Conclusions : This preliminary study suggests a potentially novel strategy for non-invasive imaging of neoangiogenesis in atherosclerotic plaque and may allow identification of unstable plaques.

scholarly journals Sustained Acceleration in Carotid Atherosclerotic Plaque Progression With Intraplaque Hemorrhage

2012 ◽  
Vol 5 (8) ◽  
pp. 798-804 ◽  
Author(s):  
Jie Sun ◽  
Hunter R. Underhill ◽  
Daniel S. Hippe ◽  
Yunjing Xue ◽  
Chun Yuan ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Intraplaque Hemorrhage ◽  
Plaque Progression ◽  
Carotid Atherosclerotic Plaque

scholarly journals A Prediction Tool for Plaque Progression Based on Patient-specific Multi-Physical Modeling

2020 ◽  
Author(s):  
Jichao Pan ◽  
Yan Cai ◽  
Liang Wang ◽  
Akiko Maehara ◽  
Gary S. Mintz ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Physical Modeling ◽  
Risk Index ◽  
Patient Specific ◽  
Prediction Tool ◽  
Plaque Progression ◽  
Imaging Data ◽  
Microenvironmental Factors ◽  
Unstable Plaques ◽  
Modeling Study

AbstractAtherosclerotic plaque rupture is responsible for a majority of acute vascular syndromes and this study aims to develop a prediction tool for plaque progression and rupture. Based on the follow-up coronary intravascular ultrasound imaging data, we performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression. Four main pathophysiological processes, i.e., lipid deposition, inflammatory response, migration and proliferation of smooth muscle cells (SMCs), and neovascularization were coupled based on the interactions demonstrated by experimental and clinical observations. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. The heterogeneity of plaque microenvironment for each patient was demonstrated by the growth curves of the main microenvironmental factors. The possible plaque developments were predicted by incorporating the systematic index with microenvironmental indicators. Five microenvironmental factors (LDL, ox-LDL, MCP-1, SMC, and foam cell) showed significant differences between stable and unstable group (p < 0.01). The inflammatory microenvironments (monocyte and macrophage) had negative correlations with the necrotic core (NC) expansion in the stable group, while very strong positive correlations in unstable group. The inflammatory microenvironment is strongly correlated to the NC expansion in unstable plaques, suggesting that the inflammatory factors may play an important role in the formation of a vulnerable plaque. This prediction tool will improve our understanding of the mechanism of plaque progression and provide a new strategy for early detection and prediction of high-risk plaques.Author summaryBesides the traditional systematic factors, the influences of the local microenvironmental factors on atherosclerotic plaque progression have been demonstrated. Mathematical and computational modeling is an important tool to investigate the complex interplay between plaque progression and the microenvironment, and provides a potential way toward the prediction of plaque vulnerability according to the comprehensive evaluation of both morphological and/or biochemical factors in tissue level with microenvironmental factors in cellular level. We performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression and predicted the possible plaque developments. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. Based on patient-specific imaging data, the mathematical model will provide a novel method to predict the changes of plaque microenvironment and improve ability to access the personal therapeutic strategy for atherosclerotic plaque.

scholarly journals Therapies Targeted at Non-Coding RNAs in Prevention and Limitation of Myocardial Infarction and Subsequent Cardiac Remodeling—Current Experience and Perspectives

2021 ◽  
Vol 22 (11) ◽  
pp. 5718
Author(s):  
Michal Kowara ◽  
Sonia Borodzicz-Jazdzyk ◽  
Karolina Rybak ◽  
Maciej Kubik ◽  
Agnieszka Cudnoch-Jedrzejewska
Keyword(s):  
Myocardial Infarction ◽  
Atherosclerotic Plaque ◽  
Cardiac Remodeling ◽  
Therapeutic Option ◽  
Circular Rna ◽  
Plaque Progression ◽  
Cardiac Damage ◽  
Non Coding Rna ◽  
Causes Of Mortality ◽  
Long Non Coding Rna

Myocardial infarction is one of the major causes of mortality worldwide and is a main cause of heart failure. This disease appears as a final point of atherosclerotic plaque progression, destabilization, and rupture. As a consequence of cardiomyocytes death during the infarction, the heart undergoes unfavorable cardiac remodeling, which results in its failure. Therefore, therapies aimed to limit the processes of atherosclerotic plaque progression, cardiac damage during the infarction, and subsequent remodeling are urgently warranted. A hopeful therapeutic option for the future medicine is targeting and regulating non-coding RNA (ncRNA), like microRNA, circular RNA (circRNA), or long non-coding RNA (lncRNA). In this review, the approaches targeted at ncRNAs participating in the aforementioned pathophysiological processes involved in myocardial infarction and their outcomes in preclinical studies have been concisely presented.

scholarly journals Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

2018 ◽  
Vol 5 (3) ◽  
pp. 171447 ◽  
Author(s):  
R. Xing ◽  
A. M. Moerman ◽  
Y. Ridwan ◽  
M. J. Daemen ◽  
A. F. W. van der Steen ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Mouse Model ◽  
Atherosclerotic Plaque ◽  
Proximal Part ◽  
Plaque Progression ◽  
Plaque Composition ◽  
Spatial Changes ◽  
Temporal And Spatial ◽  
Wall Shear

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE −/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition.

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