scholarly journals Significance of Hemodynamics Biomarkers, Tissue Biomechanics and Numerical Simulations in the Pathogenesis of Ascending Thoracic Aortic Aneurysms

2020 ◽  
Vol 26 ◽  
Author(s):  
Salvatore Campisi ◽  
Raja Jayendiran ◽  
Francesca Condemi ◽  
Magalie Viallon ◽  
Pierre Croisille ◽  
...  
Keyword(s):  
Aortic Wall ◽  
Aortic Rupture ◽  
Scientific Evidence ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Imaging Biomarkers ◽  
Aortic Tissue ◽  
Thoracic Aortic Aneurysms ◽  
Non Invasive ◽  
Valve Function

Abstract:: Guidelines for the treatment of aortic wall diseases are based on measurements of maximum aortic diameter. However aortic rupture or dissections do occur for small aortic diameters. Growing scientific evidence underlines the importance of biomechanics and hemodynamics in aortic disease development and progression. Wall shear stress (WWS) is an important hemodynamics marker which depends on aortic wall morphology and on the aortic valve function. WSS could be helpful to interpret aortic wall remodeling and define personalized risk criteria. The complementarity of Computational Fluid Dynamics and 4D Magnetic Resonance Imaging as tools for WSS assessment is a promising reality. The potentiality of these innovative technologies will provide maps or atlases of hemodynamics biomarkers to predict aortic tissue dysfunction. Ongoing efforts should focus on the correlation between these non-invasive imaging biomarkers and clinico-pathologic situations for the implementation of personalized medicine in current clinical practice.

Abstract 2681: Mutations in Smooth Muscle-Specific Contractile Proteins Cause Familial Thoracic Aortic Aneurysms and Dissections and Lead to Increased IGF-1 Expression

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christina L Papke ◽  
Hariyadarshi Pannu ◽  
Dong-Chuan Guo ◽  
Nili Avidan ◽  
Van Tran-Fadulu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Contractile Proteins ◽  
Dermal Fibroblasts ◽  
Aortic Aneurysms ◽  
Trophic Factors ◽  
Aortic Tissue ◽  
Thoracic Aortic Aneurysms ◽  
Protein Levels ◽  
Tgf Β1

Aortic aneurysms and dissections are the most common disorders affecting the aorta, and are a major cause of morbidity and mortality in the United States. Familial thoracic aortic aneurysms and dissections (FTAAD) are inherited in an autosomal dominant manner with variable expression and decreased penetrance. The disorder is genetically heterogeneous with four loci and three genes identified. Mutations in either TGFBR2 , encoding the transforming growth factor β (TGF-β) type II receptor, or MYH11 , encoding the smooth muscle cell (SMC)-specific β-myosin heavy chain, were previously found to cause FTAAD. Recently, positional cloning identified smooth muscle α-actin ( ACTA2 ) mutations as a novel cause in 10% of FTAAD. Mutations in ACTC and MYH7 cause hypertrophic cardiomyopathy (HCM), characterized by myocyte disarray and upregulation of mitotic and trophic factors. Histologic examination of aortic tissue from patients with ACTA2 (n = 6) and MYH11 (n = 2) mutations revealed SMC disarray in the aortic media similar to that seen in HCM. Furthermore, we hypothesized that mutations in ACTA2 and MYH11 cause a similar increase of mitotic and trophic factors in SMCs. The expression of two factors known to be increased in HCM, TGF-β1 and insulin-like growth factor 1 (IGF-1), were analyzed in patients’ aortic SMCs and dermal myofibroblasts. No changes in TGF-β1 were found; however, both mRNA, as measured by Q-PCR (p<0.05), and protein levels, as assessed by immunostaining, of IGF-1 were markedly increased in MYH11 and two ACTA2 mutant SMCs and aortic tissue compared with control SMCs and tissue. Differentiation of dermal fibroblasts into myofibroblasts was accomplished using TGF-β1 treatment; myofibroblast differentiation was confirmed by assessing α-actin mRNA and protein levels in untreated vs. TGF-β1-treated fibroblasts. Upon differentiation, patients’ myofibroblasts (n = 3) demonstrated increased IGF-1 expression compared with controls (p<0.05), similar to the increased IGF-1 expression by SMCs. In conclusion, IGF-1 secretion is increased in response to defects in SMC contractile proteins in SMCs and myofibroblasts. Future studies will clarify the role of IGF-1 in FTAAD and identify the pathways leading to increased IGF-1 expression.

Abstract 667: The Role of Aortic Wall-Nuclear Factor- kappa B (NF-kB) Signaling in Formation of Dissecting Aortic Aneurysms

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Talha Ijaz ◽  
Hong Sun ◽  
Adrian Recinos ◽  
Ronald G Tilton ◽  
Allan R Brasier
Keyword(s):  
Flow Cytometry ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Wall ◽  
Aortic Rupture ◽  
Aortic Aneurysms ◽  
Tunel Staining ◽  
Abdominal Aortic ◽  
Significant Difference

Introduction: Abdominal aortic aneurysm is a devastating disease since it can lead to aortic rupture and instantaneous death. We previously demonstrated that IL-6 secreted from the aortic wall is necessary for the development of abdominal aortic aneurysm and dissection (AAD). Since IL-6 is a NF-kB/RelA dependant gene, we investigated the role of aortic wall- NF-kB/RelA signaling in the development of AAD. Methods and Results: To test the role of aortic wall-RelA, we utilized Cre-Lox technology to delete RelA from aortic cells. Tamoxifen-inducible, Col1a2-promoter driven Cre mice (Col1a2-Cre) were crossed with mT/mG Cre-reporter mice to determine which aortic cells undergo genetic recombination after Cre activation. Flow cytometry analysis of the aortic wall indicated that 88% of the genetically recombined cells were SMCs and 8% were fibroblasts. Next, RelA floxed (RelA f/f) mice, generated in our lab, were crossed with Col1a2-Cre mice. RelA f/f Cre+ and RelA f/f Cre- were stimulated with tamoxifen for 10 days to generate aortic-RelA deficient (Ao-RelA-/-) or wild-type (Ao-RelA+/+) transgenics. Flow cytometry, qRT-PCR, and immunohistochemistry analysis suggested a depletion of aortic-RelA greater than 60%. To test the role of Ao-RelA in AAD, Ao-RelA -/- (n= 20) and Ao-RelA +/+ (n=14) mice were infused with angiotensin II for 7 days. Surprisingly, 20% of Ao-RelA-/- mice died from development of AAD and aortic rupture while no deaths were observed in Ao-RelA+/+ group. In addition, 40% of Ao-RelA-/- mice developed AAD compared to 14% of Ao-RelA+/+ mice. There was no significant difference in TUNEL staining or ERTR7+ fibroblast population between the two groups. Conclusion: Our studies suggest that aortic wall-RelA may be necessary for protection from AAD.

scholarly journals Arterial hypertension and aortic root dilatation: an unsolved mystery

2013 ◽  
pp. 6-11
Author(s):  
Alberto Milan ◽  
Francesco Tosello ◽  
Sara Abram ◽  
Ambra Fabbri ◽  
Alessandro Vairo ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Thoracic Aorta ◽  
Aortic Root ◽  
Aortic Wall ◽  
Aortic Aneurysms ◽  
Published Data ◽  
Thoracic Aortic Aneurysms ◽  
Biological Variables ◽  
Aortic Root Dilatation ◽  
Active Debate

Introduction: Acute and chronic aortic syndromes are associated with substantial morbidity and mortality. Silent risk factors such as arterial hypertension and aortic root dilatation can increase the likelihood of aortic dissection or rupture. The relationship between arterial hypertension and the dimensions of the aortic root dimension is a topic of active debate. Materials and methods: We reviewed the literature on the physiopathology, diagnosis, natural history, and management of thoracic aortic aneurysms. Results: Biological variables influencing the size of the aorta include age, sex, body surface area, pressure values, and stroke volume. Pathologic enlargement of the thoracic aorta can be caused by genetic, degenerative, inflammatory, traumatic, or toxic factors. Studies investigating the correlation between aortic dimensions and arterial pressures (diastolic, systolic, or pulse) have produced discordant results. Discussion: Classically, emphasis has been placed on the importance of hypertension-related degeneration of the medial layer of the aortic wall, which leads to dilatation of the thoracic aorta, reduced aortic wall compliance, and increased pulse pressures. However, there are no published data that demonstrate unequivocally the existence of a pathogenetic correlation between arterial hypertension and aortic root dilatation. Furthermore, there is no evidence that antihypertensive therapy is effective in the management of nonsyndromic forms of aortic root dilatation. An interesting branch of research focuses on the importance of genetic predisposition in the pathogenesis of thoracic aortic aneurysms. Different genetic backgrounds could explain differences in the behaviour of aortic walls exposed to the same hemodynamic stress. Further study is needed to evaluate these focal physiopathological aspects.

SMAD3 pathogenic variants: risk for thoracic aortic disease and associated complications from the Montalcino Aortic Consortium

2019 ◽  
Vol 56 (4) ◽  
pp. 252-260 ◽  
Author(s):  
Ellen M Hostetler ◽  
Ellen S Regalado ◽  
Dong-Chuan Guo ◽  
Nadine Hanna ◽  
Pauline Arnaud ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Cumulative Risk ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Disease ◽  
Thoracic Aortic Aneurysms ◽  
Missense Variants ◽  
Variant Type ◽  
Pathogenic Variants ◽  
Reduced Penetrance

BackgroundPathogenic variants in SMAD3 cause thoracic aortic aneurysms and dissections, along with aneurysms and rupture of other arteries. Here, we examined differences in clinical presentation of aortic events (dissection or surgical repair of an aneurysm) with respect to age and variant type in an international cohort of individuals with SMAD3 variants.MethodsAortic status and events, vital status and clinical features were abstracted through retrospective review of medical records of 212 individuals with 51 unique SMAD3 variants, including haploinsufficiency (HI) and missense substitutions in the MH2 domain, as well as novel in-frame deletions and missense variants in the MH1 domain.ResultsAortic events were documented in 37% of cases, with dissections accounting for 70% of events. The median age at first aortic event was significantly lower in individuals with SMAD3 MH2 missense variants than those with HI variants (42years vs 49 years; p=0.003), but there was no difference in frequency of aortic events by variant type. The cumulative risk of an aortic event was 50% at 54 years of age. No aortic events in childhood were observed.ConclusionsSMAD3 pathogenic variants cause thoracic aortic aneurysms and dissections in the majority of individuals with variable age of onset and reduced penetrance. Of the covariates examined, the type of underlying SMAD3 variant was responsible for some of this variation. Later onset of aortic events and the absence of aortic events in children associated with SMAD3 variants support gene-specific management of this disorder.

Penetration Mechanics of Endovascular Stent Graft Barbs in Aortic Tissue

2011 ◽  
Author(s):  
Kathleen Lin ◽  
Benjamin Berkowitz ◽  
Madhavan L. Raghavan
Keyword(s):  
Stent Graft ◽  
Aortic Wall ◽  
Soft Tissues ◽  
The Body ◽  
Aortic Aneurysms ◽  
Fixation Strength ◽  
Aortic Tissue ◽  
Endovascular Stent ◽  
Penetration Mechanics ◽  
The Relationship

Endovascular stent grafts with barbs — tiny needle-like pins that provide active fixation — are increasingly used for treating aortic aneurysms and dissections. Characterization of barb penetration mechanics may help improve stent-graft designs. Barb angle varies among manufacturers (10–50°). But little is known regarding aortic wall penetration characteristics in relationship to barb angle. There is a body of work on needle insertion properties such as insertion forces into soft tissues. However, there have not been specific studies involving the aorta and the relationship between entry angle and entry force. Kratzberg et al. [1,2] demonstrated that barb angle was closely related to penetration angle and that lower angles between the barb and the body of the aortic stent-graft resulted in better penetration probability and fixation strength in the aortic wall. In order to assess why lower barb angles (i.e., barb axis closer to the graft axis) resulted in better penetration, this study investigates the relationship between barb penetration angle and aortic tissue entry force and compared it to a homogeneous control membrane made of silicone.

Thoracic aortic aneurysms and other conditions

2016 ◽  
Author(s):  
Demosthenes G. Katritsis ◽  
Bernard J. Gersh ◽  
A. John Camm
Keyword(s):  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Thoracic Aortic Disease ◽  
Thoracic Aortic Aneurysms

Thoracic aortic aneurysms, aortic atheroembolic disease, and other cardiovascular conditions associated with thoracic aortic disease are discussed.

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.

scholarly journals Hypertension overrides the protective effect of female hormones on the development of aortic aneurysm secondary to Alk5 deficiency via ERK activation

2015 ◽  
Vol 308 (2) ◽  
pp. H115-H125 ◽  
Author(s):  
Bradley M. Schmit ◽  
Pu Yang ◽  
Chunhua Fu ◽  
Kenneth DeSart ◽  
Scott A. Berceli ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Aortic Aneurysm ◽  
Aortic Rupture ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Molecular Signature ◽  
Type I ◽  
Protective Effects ◽  
Female Hormones ◽  
Aortic Pathology

The prevalence of aortic aneurysm is five times higher in men than women among the general population. Similar sexual dimorphism also exists in syndromic aortic aneurysms triggered by TGF-β signaling disorders. To understand the responsible mechanisms, we developed an animal model where inducible deletion of the type I TGF-β receptor, Alk5, specifically in smooth muscle cells ( Alk5 iko) causes spontaneous aortic aneurysm formation. This model recapitulated an extreme scenario of the dimorphism in aortic aneurysm development between genders. In a comparative experiment, all Alk5 iko males ( n = 42) developed aortic aneurysms and 26% of them died prematurely from aortic rupture. In contrast, the Alk5 iko females ( n = 14) presented only a subclinical phenotype characteristic of scarcely scattered elastin breaks. Removal of male hormones via orchiectomy ( n = 7) resulted in only minimal influence on aortic pathology. However, reduction of female hormones via ovariectomy ( n = 15) increased the phenotypic penetrance from zero to 53%. Finally, an elevation of systolic blood pressure by 30 points unmasked the subclinical phenotype of Alk5 iko females ( n = 17) to 59%. This exaggerated phenotypic penetrance was coupled with an early intensification of ERK signaling, a molecular signature that correlated to 100% phenotypic penetrance in normotensive Alk5 iko males. In conclusion, aortic aneurysm induced by Alk5 iko exhibits dimorphic incidence between genders with females less susceptible to aortic disease. This sexual dimorphism is partially the result from the protective effects of female hormones. Hypertension, a known risk factor for aortic aneurysm, is able to break the female sex protective effects through mechanisms associated with enhanced ERK activity.

scholarly journals Acute aortic rupture in a dog with spirocercosis following the administration of medetomidine : clinical communication

2005 ◽  
Vol 76 (3) ◽  
Author(s):  
K.E. Joubert ◽  
M.J. McReynolds ◽  
F. Strydom
Keyword(s):  
Aortic Wall ◽  
Aortic Rupture ◽  
Clinical Signs ◽  
Diagnostic Procedures ◽  
Definitive Diagnosis ◽  
Aortic Aneurysms ◽  
Post Mortem ◽  
Clinical Communication ◽  
Acute Rupture ◽  
Strong Suspicion

Spirocercosis is an emerging disease in veterinary medicine. A strong suspicion of spirocercosis is usually evident after a thorough clinical examination and radiography of the chest has been performed. Lesions seen on radiography include an oesophageal mass, spondylitis and oesophageal air. Unfortunately, radiography is not diagnostic and additional diagnostic procedures are required to confirm the diagnosis. Endoscopy is commonly performed to diagnose the condition. The dog presented in this study had radiographic and clinical signs consistent with spirocercosis and definitive diagnosis was required. Shortly after sedation with medetomidine, the dog went into cardiac arrest and failed to respond to resuscitative measures. On post mortem, the diagnosis of spirocercosis was confirmed and the cause of death was identified as acute aortic rupture. Aortic aneurysms are not an uncommon finding and cause of acute death in dogs with spirocercosis. The acute rupture of the aorta in this case is most probably the result of cardiovascular changes associated with the administration of medetomidine. Medetomidine causes an acute rise in systemic vascular resistance with hypertension. The increase in shear stress across the weakened aortic wall resulted in rupture. Caution with the use of medetomidine in patients with spirocercosis is advised.

scholarly journals Comparative Study of Aortic Wall Stress According to Geometric Parameters in Abdominal Aortic Aneurysms

2021 ◽  
Vol 11 (7) ◽  
pp. 3195
Author(s):  
Ji-Hun You ◽  
Chung Won Lee ◽  
Up Huh ◽  
Chi-Seung Lee ◽  
Dongman Ryu
Keyword(s):  
Aortic Rupture ◽  
Wall Stress ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Factors Affecting ◽  
Abdominal Aortic ◽  
Geometric Factors ◽  
Measurement Results ◽  
Simulation Scenario ◽  
Peak Wall Stress

In abdominal aortic aneurysm (AAA), the rupture of the aortic tissue is directly related to wall stress. Thus, the investigation of maximum wall stress is a necessary procedure to predict the aortic rupture in AAA. In this study, computational simulations were performed to investigate the correlation between peak wall stress (PWS) and AAA geometry. The Holzapfel model and various orientations of the collagen fibers and thicknesses of the layers of the aorta were employed in the simulation. The material constants used in the Holzapfel model were estimated from the examination and analysis of the biaxial tensile test results of the normal abdominal aorta and AAA. The aneurysm diameter, height, neck angle, and iliac angle were selected as geometric factors affecting the AAA rupture. In addition, a simulation scenario was conceived and created based on the measurement results using the computed tomography data of patients with AAA. Accordingly, the correlation between the PWS and AAA geometry was estimated.

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