Abstract 105: Association of Viscoelastic Material Properties and Extracellular Matrix Remodeling in Human Abdominal Aortic Aneurysmal Tissue

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Doran S Mix ◽  
Sandra A Toth ◽  
Ibrahima Bah ◽  
Michael C Stoner ◽  
Bruce I Goldman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Western Blot ◽  
Viscoelastic Material ◽  
Material Properties ◽  
Aortic Wall ◽  
Cyclic Strain ◽  
Wall Stress ◽  
Aortic Tissue ◽  
Matrix Remodeling ◽  
Abdominal Aortic

Objectives: Predicting rupture of abdominal aortic aneurysm (AAA) requires knowledge of both the rate of extracellular matrix (ECM) degradation and the pulsatile stress on the aortic tissue. The activity of matrix metallopeptidase 9 (MMP9) and its inhibitor, TIMP1, are associated with alterations in aortic ECM but it is unknown if these changes effect the dynamic viscoelastic properties. We hypothesize that increased levels of MMP9 within AAA tissue will be associated with a greater dynamic modulus (E*), as a surrogate of increased aortic wall stress. Methods: Human aneurysmal aortic tissue was obtained at the time of open AAA repair (n=11) and age-matched non-aneurysmal cadavers (n=10). Uniaxial viscoelastic material properties were measured in the circumferential orientation under physiologic preload (110 mmHg) and cyclic strain (± 5%@1Hz). Quantitative histologic and immunohistochemistry were preformed using Fiji imaging software. Aortic MMP9 and TIMP1 content and activity were quantified using western blot and zymography. Results: E* was greater (1862±464 vs 1362±405 kPa, p=0.02) in the AAA tissue as compared to non-aneurysmal tissue. AAA tissue contained less elastin (6.7±6.7 vs 23.4±8.7%, p=0.01) and a greater collagen/elastin ratio (19.9±20.6 vs 2.3±2.5%, p=0.05). Immunohistochemistry revealed 200% greater MMP9 content in the AAA tissue (Figure A & B, 0.61 vs 0.03%, p=0.03). Increased MMP9 content was confirmed using a western blot (0.43 vs 0.06 AU, p<0.01). No difference in relative MMP9 activity (4307 vs 2324 AU, p=0.25) or level of TIMP1 (0.03 vs 0.02, p=0.6) were observed. There was a positive linear correlation (Figure C, r 2 =0.47) between E* and MMP9 as determined by quantitative immunohistochemistry. Conclusions: Our data suggests a positive relationship between E* and MMP9 content. Increased tissue stiffness may trigger MMP9 production resulting in a positive-feedback loop, progressively increasing aortic wall stress and rupture risk.

Abstract 135: Thoracic Aortic Wall Tension Regulates microRNA-133a Abundance

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Adam W Akerman ◽  
Elizabeth K Nadeau ◽  
Robert E Stroud ◽  
Rupak Mukherjee ◽  
John S Ikonomidis ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Wall ◽  
Ex Vivo ◽  
Cyclic Stretch ◽  
Aortic Tissue ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Wall Tension ◽  
Wild Type

Background: MicroRNA-133a (miR133a) is a small non-coding RNA, which represses the translation of multiple mRNAs. This laboratory has reported an inverse relationship between aortic diameter and miR133a abundance in aortic tissue from patients with thoracic aortic aneurysm (TAA); as diameter increased, the abundance of miR133a decreased. Given that wall tension at a given pressure increases with increasing vessel diameter (Law of LaPlace), this study tested the hypothesis that elevated aortic wall tension results in a loss of miR-133a. Methods/Results: TAA was induced in wild type mice using an established murine model (0.5M CaCl 2 application, 15 min). MiR133a abundance (QPCR) was reduced in TAA tissue (3-wk TAA, 42.1±8.6% p<0.05 vs mice without TAA (100%)). In two in vivo models of elevated wall tension ( simulated hypertension ): 1) ANGII (angiotensin II infusion; 1.44mg/kg/day), and 2) BPH2 (spontaneously hypertensive mice, The Jackson Laboratory, Stock #003005), miR133a levels were decreased compared to normotensive controls (ANGII: 53.0±4.3%; BPH2: 51.7±7.0%; p<0.05 vs normotensive control (100%)). Aortic rings from wild type mice were hung on parallel wires in an ex vivo tissue myograph at 0.7 g, then ANGII (100nM) was added to the tissue baths, which generated increased tension (1.21±0.15g) and resulted in reduced tissue miR133a abundance (46.0±12%; p<0.05 vs no AngII,). Furthermore, increased tension alone (1.5g, 3 hr) resulted in decreased tissue miR133a abundance (39.0±7.0%; p<0.05 vs 0.7 g tension). Isolated primary aortic cell lines (fibroblasts (FB) and smooth muscle cells (SMC)) were exposed to biaxial cyclic stretch for 3 hr. FB miR133a was reduced (62.8±8.3%; p<0.05 vs unstretched control (100%)), while SMC miR133a abundance remained unchanged. Conclusion: The significance of these unique findings is 2-fold: First, tension alone was sufficient to decrease miR133a abundance in aortic tissue. Second, increased tension reduced miR133a abundance in FB, a cell type that is responsible for extracellular matrix remodeling. These findings suggest changes in wall tension alone ( hypertension ) may be associated with pathological extracellular matrix remodeling, in part, through the loss of miR133a in fibroblasts.

Abstract 297: Segmental Aortic Stiffening is a Mechanism Driving Early Abdominal Aortic Aneurysm Pathogenesis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Uwe Raaz ◽  
Alexander M Zöllner ◽  
Ryuji Toh ◽  
Futoshi Nakagami ◽  
Isabel N Schellinger ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Wall ◽  
Ex Vivo ◽  
Wall Stress ◽  
Finite Elements Analysis ◽  
External Application ◽  
Abdominal Aortic ◽  
Aneurysm Growth ◽  
Aortic Stiffening

Stiffening of the aortic wall is a phenomenon consistently observed in abdominal aortic aneurysm (AAA). However, its role in AAA pathophysiology is largely undefined. Using an established murine elastase-induced AAA model, we demonstrate that segmental aortic stiffening (SAS) precedes aneurysm growth. Finite elements analysis (FEA)-based wall stress calculations reveal that early stiffening of the aneurysm-prone aortic segment leads to axial (longitudinal) stress generated by cyclic (systolic) tethering of adjacent, more compliant wall segments. Interventional stiffening of AAA-adjacent segments (via external application of surgical adhesive) significantly reduces aneurysm growth. These changes correlate with reduced segmental stiffness of the AAA-prone aorta (due to equalized stiffness in adjacent aortic segments), reduced axial wall stress, decreased production of reactive oxygen species (ROS), attenuated elastin breakdown, and decreased expression of inflammatory cytokines and macrophage infiltration, as well as attenuated apoptosis within the aortic wall. Cyclic pressurization of stiffened aortic segments ex vivo increases the expression of genes related to inflammation and extracellular matrix (ECM) remodeling. Finally, human ultrasound studies reveal that aging, a significant AAA risk factor, is accompanied by segmental infrarenal aortic stiffening. The present study introduces the novel concept of segmental aortic stiffening (SAS) as an early pathomechanism generating aortic wall stress and thereby triggering AAA growth. Therefore monitoring SAS by ultrasound might help to better identify patients at risk for AAA disease and better predict the susceptibility of small AAA to further growth. Moreover our results suggest that interventional mechanical stiffening of the AAA-adjacent aorta may be further tested as a novel treatment option to limit early AAA growth.

Material Properties of Abdominal Aortic Aneurysm Wall From Uniaxial Tests

2000 ◽  
Author(s):  
Mano J. Thubrikar ◽  
Michel Labrosse ◽  
Jihad Al-Soudi ◽  
Brett Fowler ◽  
Francis Robicsek
Keyword(s):  
Experimental Data ◽  
Material Properties ◽  
Aortic Wall ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Modeling Tools ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Abdominal Aortic Aneurysm Wall ◽  
Mechanical Models

Abstract Abdominal aortic aneurysms (AAA) rupture when the aortic wall cannot withstand the stresses and strains induced by the pulsatile blood pressure. In recent years, different mechanical models of aneurysms have been presented (Vorp et al., 1998, Di Martino et al., 1998, Thubrikar et al., 1999). Although powerful modeling tools such as finite elements are available, there is still a need for experimental data concerning the mechanical properties of the aneurysm wall.

Increased Anterior Abdominal Aortic Wall Motion: Possible Role in Aneurysm Pathogenesis and Design of Endovascular Devices

2007 ◽  
Vol 14 (4) ◽  
pp. 574-584 ◽  
Author(s):  
Craig J. Goergen ◽  
Bonnie L. Johnson ◽  
Joan M. Greve ◽  
Charles A. Taylor ◽  
Christopher K. Zarins
Keyword(s):  
Body Mass ◽  
Wall Motion ◽  
Aortic Wall ◽  
Cyclic Strain ◽  
Posterior Wall ◽  
Anterior Wall ◽  
Dynamic Strain ◽  
Wall Displacement ◽  
Abdominal Aortic ◽  
Endovascular Devices

Purpose: To determine whether variations in aortic wall motion exist in mammalian species other than humans and to consider the potential implications of such variations. Methods: M-mode ultrasound was used to measure abdominal aortic wall motion in 4 animal species [mice (n=10), rats (n=8), rabbits (n=7), and pigs (n=5)], and humans (n=6). Anterior wall displacement, posterior wall displacement, and diastolic diameter were measured. The ratio of displacement to diameter and cyclic strain were calculated. Results: Body mass varied from 24.1±2.4 g (mouse) to 61.8±13.4 kg (human); aortic diameter varied from 0.53±0.07 mm (mouse) to 1.2±1 mm (human). Anterior wall displacement was 2.5 to 4.0 times greater than posterior among the species studied. The ratios of wall displacement to diastolic diameter were similar for the anterior (range 9.40%–11.80%) and posterior (range 2.49%–3.91%) walls among species. The ratio of anterior to posterior displacement (range 2.47–4.03) and aortic wall circumferential cyclic strain (range 12.1%–15.7%) were also similar. An allometric scaling exponent was experimentally derived relating anterior wall (0.377±0.032, R2=0.94) and posterior wall (0.378±0.037, R2=0.93) displacement to body mass. Conclusion: Abdominal aortic wall dynamics are similar in animals and humans regardless of aortic size, with more anterior than posterior wall motion. Wall displacement increases linearly with diameter, but allometrically with body mass. These data suggest increased dynamic strain of the anterior wall. Increased strain, corresponding to increased elastin fatigue, may help explain why human abdominal aortic aneurysms initially develop anteriorly. Aortic wall motion should be considered when developing endovascular devices, since asymmetric motion may affect device migration, fixation, and sealing.

Results of Autopsy 7 Months after Successful Endoluminal Treatment of an Infrarenal Abdominal Aortic Aneurysm

1995 ◽  
Vol 2 (4) ◽  
pp. 348-355 ◽  
Author(s):  
Timothy J. McGahan ◽  
Gerald A. Berry ◽  
Sarah L. McGahan ◽  
Geoffrey H. White ◽  
Weiyun Yu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Microscopic Examination ◽  
Aortic Wall ◽  
Aortic Tissue ◽  
Esophageal Rupture ◽  
Spontaneous Esophageal Rupture ◽  
Infrarenal Abdominal Aortic Aneurysm ◽  
Abdominal Aortic ◽  
Endoluminal Treatment

Purpose: To report the results of a postmortem examination in a patient who died of unrelated causes 7 months following endoluminal treatment of an infrarenal abdominal aortic aneurysm (AAA). Methods: As part of an FDA Phase I pilot study, a 73-year-old man underwent successful endoluminal exclusion of an infrarenal AAA using a 9-cm-long endograft (Endovascular Grafting System). Seven months later, he succumbed to complications of a spontaneous esophageal rupture. At autopsy, the aorta was dissected in situ by a vascular surgeon and pathologist before being explanted in order to examine the wound healing characteristics at the aorta-endograft interface. Particular attention was also directed to the hooks composing the attachment system at each end of the endograft. Results: Macroscopic and microscopic examination revealed that the graft had completely excluded the aneurysm sac from the circulation and was incorporated into the aortic wall at the proximal neck and distal cuff. A smooth pannus of endothelial cells covered the proximal end of the endograft at the areas of contact with the aorta, while microscopic examination of the distal end of the graft revealed poorly formed, fibrinous pannus. The neointima deep to the endothelium consisted of a collagenous matrix containing myofibroblasts and histiocytes, providing evidence of healing between the endograft and aorta. Both renal arteries were clear of the proximal end of the endograft, but a previously unrecognized right lower pole renal artery with an extremely caudal origin was excluded from the aortic lumen. Each hook of the attachment system was seen protruding through the adventitia of the aorta. There was no evidence of trauma to the aortic wall or the surrounding tissues caused by these hooks. Conclusion: There appears to be evidence that an endoluminally placed aortic graft may be incorporated by the host aortic tissue.

Abstract 109: Tumor Necrosis Factor Inducible Gene 6 Protein (TSG-6) is Highly Expressed in Human Abdominal Aortic Aneurysms

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
S. Keisin Wang ◽  
Linden Green ◽  
Jie Xie ◽  
Raghu Motaganahalli ◽  
Andres Fajardo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Aortic Wall ◽  
Mononuclear Cells ◽  
Tissue Concentration ◽  
Macrophage Polarization ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Abdominal Aortic ◽  
Anti Inflammatory

Objective: The formation of an abdominal aortic aneurysm (AAA) is characterized by a dominance of pro-inflammatory forces that result in smooth muscle cell apoptosis, extra-cellular matrix degradation, and progressive diameter expansion. Additional defects in the anti-inflammatory response may also contribute to AAA progression, however have yet to be characterized robustly. Here, we describe the role of the anti-inflammatory cytokine TSG-6 (TNF-stimulated gene-6) in AAA formation. Methods: Blood and aortic tissue samples were collected from patients undergoing elective AAA screening and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Cytokine concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS analysis. In vitro, macrophage polarization from monocytes were performed with young, healthy donor PBMCs. Results: TSG-6 was found to be abnormally elevated in both the plasma and aorta of patients with AAA compared to healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less diseased proximal and distal shoulders compared to the central aspect of the aneurysm. IHC localized the majority of TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed in the aortic wall, however M1/M2 ratios were unchanged from healthy controls. Additionally, we observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the anti-inflammatory M2 phenotype in vitro . Conclusions: AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to resultant vessel breakdown. From our results, we suggest TSG-6 is elevated in the AAA patient as a compensatory anti-inflammatory feedback mechanism. However, it’s effects may be abrogated by defects in CD44, its cognate receptor or downstream signaling pathways, future areas for investigation.

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