Quantifying the Structural and Mechanical Changes in Elastase Degraded Arteries as an In Vitro Model of Aortic Aneurysm

2011 ◽  
Author(s):  
Ming-Jay Chow ◽  
Jarred Raymund Mondonedo ◽  
Katherine Yanhang Zhang
Keyword(s):  
Aortic Aneurysm ◽  
Structural Changes ◽  
Strain Energy Function ◽  
Wall Stress ◽  
Aneurysm Rupture ◽  
Aortic Tissue ◽  
Clinical Practices ◽  
Abdominal Aortic ◽  
Wall Stiffness

Common characteristics of aortic aneurysm include loss of elastin/smooth muscle cells, increase in fibrillary collagen, and increase in artery diameter [5]. Because of the high mortality rate of aneurysm rupture, it is desirable to be able to predict when a patient should have surgery to repair the dilated tissue. Current clinical practices involve predicting aneurysm rupture based on artery expansion rate and diameter. However, other parameters such as wall stiffness and peak wall stress may offer better predictions as to when an aneurysm will fail [8]. Previous studies have investigated the differences in elastin and collagen content of abdominal aortic tissue with and without abdominal aortic aneurysm (AAA) [1]. In another study, human aortic aneurysm tissue was tested in a biaxial tensile tester and the resulting stress strain curves were fitted using Fung type exponential strain energy function [7]. More extensive modeling of aneurysm tissue has been done by modifying the Holzapfel model to incorporate a parameter that characterizes the tissue weakening before the failure of the inner elastic laminae, ground matrix, or collagen fibers themselves [6]. Previous studies have found compositional and mechanical differences between aneurysm and healthy tissue. In addition, good structurally based models for arteries that are developing aneurysm exist but these are mostly theoretical [6]. In order to improve aneurysm rupture prediction techniques, a better understanding of how structural changes affect the mechanical properties of the artery is necessary.

scholarly journals In vivo analysis of mechanical wall stress and abdominal aortic aneurysm rupture risk

2002 ◽  
Vol 36 (3) ◽  
pp. 589-597 ◽  
Author(s):  
Mark F. Fillinger ◽  
M.L. Raghavan ◽  
Steven P. Marra ◽  
Jack L. Cronenwett ◽  
Francis E. Kennedy
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Wall Stress ◽  
Aneurysm Rupture ◽  
Rupture Risk ◽  
Abdominal Aortic Aneurysm Rupture ◽  
Abdominal Aortic ◽  
In Vivo Analysis

scholarly journals Cyclophilin A/EMMPRIN Axis Is Involved in Pro-Fibrotic Processes Associated with Thoracic Aortic Aneurysm of Marfan Syndrome Patients

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 154 ◽  
Author(s):  
Gianluca L. Perrucci ◽  
Erica Rurali ◽  
Maria Corlianò ◽  
Maria Balzo ◽  
Michela Piccoli ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Thoracic Aortic Aneurysm ◽  
Cyclophilin A ◽  
Aortic Tissue ◽  
Tissue Samples ◽  
Abdominal Aortic ◽  
Tgf Β1 ◽  
In Vitro Treatment

Background: Marfan syndrome (MFS) is a genetic disease, characterized by thoracic aortic aneurysm (TAA), which treatment is to date purely surgical. Understanding of novel molecular targets is mandatory to unveil effective pharmacological approaches. Cyclophilin A (CyPA) and its receptor EMMPRIN are associated with several cardiovascular diseases, including abdominal aortic aneurysm. Here, we envisioned the contribution of CyPA/EMMPRIN axis in MFS-related TAA. Methods: We obtained thoracic aortic samples from healthy controls (HC) and MFS patients’ aortas and then isolated vascular smooth muscle cells (VSMC) from the aortic wall. Results: our findings revealed that MFS aortic tissue samples isolated from the dilated zone of aorta showed higher expression levels of EMMPRIN vs. MFS non-dilated aorta and HC. Interestingly, angiotensin II significantly stimulated CyPA secretion in MFS-derived VSMC (MFS-VSMC). CyPA treatment on MFS-VSMC led to increased levels of EMMPRIN and other MFS-associated pro-fibrotic mediators, such as TGF-β1 and collagen I. These molecules were downregulated by in vitro treatment with CyPA inhibitor MM284. Our results suggest that CyPA/EMMPRIN axis is involved in MFS-related TAA development, since EMMPRIN is upregulated in the dilated zone of MFS patients’ TAA and the inhibition of its ligand, CyPA, downregulated EMMPRIN and MFS-related markers in MFS-VSMC. Conclusions: these insights suggest both a novel detrimental role for CyPA/EMMPRIN axis and its inhibition as a potential therapeutic strategy for MFS-related TAA treatment.

Abdominal Aortic Aneurysm Rupture Risk Assessment Exploiting Dynamic (4D) CT Based Wall Motion Data and Finite Element Analysis

2013 ◽  
Author(s):  
Eleni Metaxa ◽  
Vasileios Vavourakis ◽  
Nikolaos Kontopodis ◽  
Konstantinos Pagonidis ◽  
Christos V. Ioannou ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Risk Estimation ◽  
Wall Stress ◽  
Aneurysm Rupture ◽  
Patient Specific ◽  
Rupture Risk ◽  
Element Analysis ◽  
Motion Data ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) disease is primarily a degenerative process, where rupture occurs when stress exerted on the aortic wall exceeds its failure strength. Therefore, knowledge of both the wall stress distribution and the mechanical properties of the AAA wall is required for patient specific rupture risk estimation.

scholarly journals The Association of Wall Mechanics and Morphology: A Case Study of Abdominal Aortic Aneurysm Growth

2011 ◽  
Vol 133 (10) ◽  
Author(s):  
Christopher B. Washington ◽  
Judy Shum ◽  
Satish C. Muluk ◽  
Ender A. Finol
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Wall Stress ◽  
Aneurysm Rupture ◽  
Maximum Diameter ◽  
Least Squares Regression ◽  
Surveillance Period ◽  
Element Analysis ◽  
Abdominal Aortic ◽  
Peak Wall Stress

The purpose of this study is to evaluate the potential correlation between peak wall stress (PWS) and abdominal aortic aneurysm (AAA) morphology and how it relates to aneurysm rupture potential. Using in-house segmentation and meshing software, six 3-dimensional (3D) AAA models from a single patient followed for 28 months were generated for finite element analysis. For the AAA wall, both isotropic and anisotropic materials were used, while an isotropic material was used for the intraluminal thrombus (ILT). These models were also used to calculate 36 geometric indices characteristic of the aneurysm morphology. Using least squares regression, seven significant geometric features (p < 0.05) were found to characterize the AAA morphology during the surveillance period. By means of nonlinear regression, PWS estimated with the anisotropic material was found to be highly correlated with three of these features: maximum diameter (r = 0.992, p = 0.002), sac volume (r = 0.989, p = 0.003) and diameter to diameter ratio (r = 0.947, p = 0.033). The correlation of wall mechanics with geometry is nonlinear and reveals that PWS does not increase concomitantly with aneurysm diameter. This suggests that a quantitative characterization of AAA morphology may be advantageous in assessing rupture risk.

An Automated Methdology for Investigating the Correlation Between Abdominal Aortic Aneurysm Wall Stress and Risk of Rupture

2001 ◽  
Author(s):  
Madhavan L. Raghavan ◽  
Mark F. Fillinger ◽  
Steven P. Marra ◽  
Francis E. Kennedy
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Wall Stress ◽  
Aneurysm Rupture ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Risk Of Rupture ◽  
Scan Data ◽  
Biomechanical Approach

Abstract Clinical experience with regard to predicting abdominal aortic aneurysm (AAA) rupture has shown that although AAA diameter is a good indicator, there are likely other risk factors. Some researchers have explored a biomechanical approach to predicting aneurysm rupture risk [1,2] based on the hypothesis that aneurysm rupture occurs when the mechanical stresses in the aortic wall exceed the wall failure strength. Therefore, knowledge of wall stresses in a particular AAA may help identify impending rupture. Recently, researchers have used patients’ abdominal CT scan data and blood pressure to estimate in-vivo AAA wall stresses [3]. In the present project, an improved automated methodology is used to predict AAA wall stress. The underlying correlation between mechanical stress and aneurysm wall rupture is also investigated.

Abstract 676: Microrna-30 and Cthrc1: Translating Aging into Vascular Stiffness and Abdominal Aortic Aneurysm

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Joshua M Spin ◽  
Wei H Zheng ◽  
Matti Adam ◽  
Uwe Raaz ◽  
Isabel Schellinger ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Calcification ◽  
Vascular Stiffness ◽  
Aortic Tissue ◽  
Down Regulation ◽  
Matrix Deposition ◽  
Age Related ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is a major source of vascular morbidity and mortality, with increasing age representing one of the strongest risk factors. While increases in aortic extra-cellular matrix deposition may be protective, changes in vessel architecture with age result in heterogeneous stiffness and vascular calcification, which appear to pre-dispose to AAA development. MicroRNAs (miRs) are key regulators of vascular homeostasis and pathobiology. Array profiling and qRT-PCR of aneurysmal aortic tissue in a murine AAA model (elastase-infused C57/B6) showed significant down-regulation of the miR-30 family, which is believed to have a role in vascular calcification. Increased age augmented this response, particularly for miR-30a, 30b and 30c. RNASeq profiling of a related AAA model (Ang-II in ApoE-/- KO) showed similar aortic down-regulation. Further, of differentially down-regulated miRs, miR-30 had the highest inverse correlation with mRNA gene targets. One predicted target - Cthrc1 (collagen triple helix repeat containing-1) - was the most consistently and significantly up-regulated gene across all time points in the AAA models. The protein resides within vascular smooth muscle cells (SMCs) and fibroblasts, responds to injury, and may regulate collagen expression and deposition. Immunofluorescence staining of AAA vs. normal aortas revealed increased expression of CTHRC1. We further found that miR-30 family members bind to the CTHRC1 3’ UTR and regulate gene expression in vitro, and that antagomir suppression of miR-30 upregulates CTHRC1 in SMCs. We also demonstrated that signaling pathways known to increase in activity with aging within the aorta, and which are associated with vascular calcification and fibrosis (e.g. IL6-based inflammatory signaling, TGF-β signaling, and BMP-2 signaling) down-regulate miR-30 family expression in SMCs, and inversely up-regulate CTHRC1 expression. Forced overexpression of miR-30 in SMC in vitro down-regulates RUNX2, a key promoter of vascular stiffness and calcification. Taken together, these results suggest a significant role for miR-30 in pathways related to matrix deposition and calcification, regulating aortic pathobiology and age-related susceptibility to AAA.

scholarly journals Osteopontin N-Terminal Function in an Abdominal Aortic Aneurysm From Apolipoprotein E-Deficient Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongyang Liu ◽  
Ying Zhang ◽  
Wei Song ◽  
Yancui Sun ◽  
Yinong Jiang
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Inflammatory Factors ◽  
Aortic Tissue ◽  
Binding Motif ◽  
Ang Ii ◽  
Histological Changes ◽  
N Protein ◽  
Abdominal Aortic

The cleavage of osteopontin (OPN) by thrombin results in an N-terminal fragment (OPN-N), which exposes a cryptic integrin-binding motif that promotes the adherence of cells, and plays a proinflammatory role. However, the effect of OPN-N on abdominal aortic aneurysm (AAA) remains unknown. The aim of this study was to investigate the expression of OPN-N in aortic tissue samples obtained from patients, who underwent acute aortic dissection (AD), and normal aorta, effect of OPN-N on angiotensin (Ang) II-induced AAA in mice, and relationship between OPN-N and pyroptosis-related inflammatory factors in vitro. Hematoxylin and eosin staining was conducted to detect histological changes. Next, we detected the expression of the OPN-N protein. Additionally, ApoE−/− mice were divided into four groups: control, control + M5Ab (to block the OPN-N function in mice), Ang II, and Ang II + M5Ab. All mice were euthanized after a 28-day infusion and whole aortas, including thoracic and abdominal aortas, were collected for morphological and histological analysis of the AAA. The OPN-N protein expression was higher in patients with AD than in normal individuals, while histological changes in the aortas of Ang II mice were suppressed in Ang II + M5Ab mice. The expression of OPN-N, NOD-, LRR-, and pyrin domain-containing protein 3, pro-Caspase-1, ASC, Gasdermin-d, interleukin (IL)-18, IL-1β, matrix metalloproteinase (MMP) 2, and MMP9 was lower in the Ang II + M5Ab group than in the Ang II group. The gene expression of monocyte chemoattractant protein-1, IL-6, and tumor necrosis factor-α was suppressed in the aortic tissues of the Ang II + M5Ab group compared with the Ang II group. Moreover, the expression of α-smooth muscle actin was lower in the Ang II group than in the Ang II + M5Ab group. In vitro results showed that the increase in the expression of pyroptosis-related inflammatory factors induced by OPN was mediated through the nuclear factor (NF)-κB pathway. In conclusion, OPN-N promotes AAA by increasing the expression of pyroptosis-related inflammatory factors through the NF-κB pathway, inflammation, and extracellular matrix degradation. These results highlight the potential of OPN-N as a new therapeutic target to prevent AAA expansion.

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