scholarly journals Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms

2017 ◽  
Vol 14 (130) ◽  
pp. 20161036 ◽  
Author(s):  
C. Bellini ◽  
M. R. Bersi ◽  
A. W. Caulk ◽  
J. Ferruzzi ◽  
D. M. Milewicz ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Structural Integrity ◽  
Ascending Aorta ◽  
Elastic Fibre ◽  
Cytoskeletal Proteins ◽  
Aortic Aneurysms ◽  
Genetic Mutations ◽  
Murine Models ◽  
Thoracic Aortic Aneurysms ◽  
Signalling Molecules

Thoracic aortic aneurysms are life-threatening lesions that afflict young and old individuals alike. They frequently associate with genetic mutations and are characterized by reduced elastic fibre integrity, dysfunctional smooth muscle cells, improperly remodelled collagen and pooled mucoid material. There is a pressing need to understand better the compromised structural integrity of the aorta that results from these genetic mutations and renders the wall vulnerable to dilatation, dissection or rupture. In this paper, we compare the biaxial mechanical properties of the ascending aorta from 10 murine models: wild-type controls, acute elastase-treated, and eight models with genetic mutations affecting extracellular matrix proteins, transmembrane receptors, cytoskeletal proteins, or intracellular signalling molecules. Collectively, our data for these diverse mouse models suggest that reduced mechanical functionality, as indicated by a decreased elastic energy storage capability or reduced distensibility, does not predispose to aneurysms. Rather, despite normal or lower than normal circumferential and axial wall stresses, it appears that intramural cells in the ascending aorta of mice prone to aneurysms are unable to maintain or restore the intrinsic circumferential material stiffness, which may render the wall biomechanically vulnerable to continued dilatation and possible rupture. This finding is consistent with an underlying dysfunctional mechanosensing or mechanoregulation of the extracellular matrix, which normally endows the wall with both appropriate compliance and sufficient strength.

Cannulation of the Ascending Aorta in Left Thoracotomy for Thoracic Aortic Aneurysms

2007 ◽  
Vol 10 (1) ◽  
pp. E81-E83 ◽  
Author(s):  
Riza Turkoz ◽  
Oner Gulcan ◽  
Orhan Demirturk ◽  
Ayda Turkoz
Keyword(s):  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Left Thoracotomy ◽  
Thoracic Aortic Aneurysms

scholarly journals Quantitative not qualitative histology differentiates aneurysmal from nondilated ascending aortas and reveals a net gain of medial components

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sameh Yousef ◽  
Nana Matsumoto ◽  
Issam Dabe ◽  
Makoto Mori ◽  
Alden B. Landry ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Quantitative Assessment ◽  
Cell Number ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Adaptive Responses ◽  
Cross Sectional ◽  
Thoracic Aortic Aneurysms ◽  
Medial Degeneration ◽  
The Media

AbstractMedial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

scholarly journals Giant Aortic Aneurysm in Child with Cutis Laxa Syndrome: Unusual Presentation, New Surgical Technique

2021 ◽  
Vol 24 (6) ◽  
pp. E1054-E1056
Author(s):  
Mazen Shamsaldeen Faden ◽  
Nada Ahmed Noaman ◽  
Osman Osama Osman Osama ◽  
Ahmed Abdelrahman Elassal ◽  
Arwa Mohammed Al-ghamdi ◽  
...  
Keyword(s):  
Final Diagnosis ◽  
Ascending Aorta ◽  
Accurate Diagnosis ◽  
Aortic Aneurysms ◽  
Cutis Laxa ◽  
Descending Aorta ◽  
Aorta Aneurysm ◽  
Thoracic Aortic Aneurysms ◽  
Valvular Insufficiency ◽  
New Surgical Technique

Ascending thoracic aortic aneurysms are rare in childhood and typically are seen in the setting of connective tissue defect syndromes. These aneurysms may lead to rupture, dissection, or valvular insufficiency, so root replacement is recommended. Here, we present a 17-month-old girl who presented with fever, cough, and pericardial effusion. Initially, we suspected this could be a COVID-19 case, so a nasopharyngeal swap was performed. An ascending aorta aneurysm involving the aortic arch was confirmed by echo, and urgent ascending aorta and arch replacement were done by utilizing the descending aorta as a new arch. The final diagnosis came with cutis laxa syndrome. In similar cases, good outcomes can be achieved with accurate diagnosis and appropriate surgical management.

scholarly journals 2464 Sexual dimorphism in a mouse model of syndromic thoracic aortic aneurysm

2018 ◽  
Vol 2 (S1) ◽  
pp. 27-27
Author(s):  
Zheying Chen ◽  
Alan Daugherty ◽  
Mary Sheppard
Keyword(s):  
Extracellular Matrix ◽  
Sexual Dimorphism ◽  
Mouse Model ◽  
Aortic Aneurysms ◽  
Pcr Analysis ◽  
Wild Type ◽  
Aortic Dilation ◽  
Male And Female ◽  
Thoracic Aortic Aneurysms ◽  
Male Sex

OBJECTIVES/SPECIFIC AIMS: Pre-clinical and clinical observations have noted that increased aortic dilation is associated with male sex. Using an experimental model of severe, syndromic thoracic aortic aneurysms, we quantify aortic dilation and elastin stability in male Versus female mice. METHODS/STUDY POPULATION: Ascending aortas from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. At termination, aortas were harvested for RT-PCR analysis of extracellular matrix genes. Aortas were serially sectioned and elastin fragmentation was imaged by auto-fluorescence. RESULTS/ANTICIPATED RESULTS: At 12 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice were significantly different (2.24±0.43 vs. 1.57±0.22 mm; p=0.002), while there were no significant differences between sexes of wild type littermates (1.29±0.13 vs. 1.23±0.08 mm; p=0.71). Male sex was associated with increased elastin but not fibrillin-1 mRNA expression. Ascending aortas from male and female FBN1mgR/mgR mice significantly differed in the degree of elastin fragmentation (2.76 vs. 1.85 breaks/ 100 µm aorta; p=0.03). DISCUSSION/SIGNIFICANCE OF IMPACT: Sexual dimorphism of thoracic aortic dilation observed in human TAA patients was recapitulated in the fibirllin-1 hypomorphic mouse model of syndromic thoracic aortic aneurysms. Differences in this mouse model could be explained by the differential expression of extracellular matrix genes.

scholarly journals Primary Lymphoma Presenting in an Ascending Aortic Aneurysm: A Case Report

Aorta ◽  
2020 ◽  
Vol 08 (02) ◽  
pp. 038-040
Author(s):  
Alexander M. Schurman ◽  
David Mendoza ◽  
Chris K. Rokkas
Keyword(s):  
Management Strategies ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Prior History ◽  
Primary Lymphoma ◽  
Surgical Specimen ◽  
Hematological Disorders ◽  
Thoracic Aortic Aneurysms ◽  
Asymptomatic Patients ◽  
History Of

AbstractSmall lymphocytic lymphoma (SLL) is rarely associated with thoracic aortic aneurysms. Aneurysm of the ascending aorta associated with SLL has never been reported before. We describe the case of an asymptomatic 68-year-old woman who presented with a 5.5-cm aneurysm of the ascending aorta and no prior history of hematological disorders. Following excision and repair, the surgical specimen showed infiltration of the aortic wall by lymphocytes, expressing markers consistent with SLL. While symptomatic SLL carries a poor prognosis, risk stratification tools are applied to guide management strategies in asymptomatic patients.

Ascending Thoracic Aorta Exhibits Anisotropic Failure Behavior in Shear Lap Testing

2013 ◽  
Author(s):  
Colleen Witzenburg ◽  
Sachin Shah ◽  
Hallie P. Wagner ◽  
Janna Goodrich ◽  
Victor H. Barocas
Keyword(s):  
Arterial Pressure ◽  
Mechanical Behavior ◽  
Thoracic Aorta ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Failure Behavior ◽  
Thoracic Aortic Aneurysms ◽  
Wall Strength ◽  
Imminent Death ◽  
Aneurysm Dissection

Aneurysm dissection and rupture, resulting in imminent death, is the primary risk associated with thoracic aortic aneurysms (TAA). Nearly 60% of TAA involves the ascending aorta [1]. Dissection and rupture occur when the remodeled tissue is no longer able to withstand the stresses generated by the arterial pressure. As the ascending TAA grows, however, changes in its mechanical behavior, particularly wall strength, are unknown.

Ascending aorta mechanics in bicuspid aortopathy: controversy or fact?

2020 ◽  
pp. 021849232092873
Author(s):  
Dimitrios C Iliopoulos ◽  
Dimitrios P Sokolis
Keyword(s):  
Mechanical Properties ◽  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Aged Patients ◽  
Thoracic Aortic Aneurysms ◽  
Maximal Diameter ◽  
Sole Criterion

Bicuspid aortic valve is the most common congenital cardiovascular defect, often associated with proximal aortic dilatation, and the ideal management strategy is debated. The inconsistency in previous and present guideline recommendations emphasizes the insufficiency of the maximal diameter as the sole criterion for prophylactic repair. Our ability to guide clinical decisions may improve through an understanding of the mechanical properties of ascending thoracic aortic aneurysms in bicuspid compared to tricuspid aortic valve patients and non-aneurysmal aortas, because dissection and rupture are aortic wall mechanical failures. Such an understanding of the mechanical properties has been attempted by several authors, and this article addresses whether there is a controversy in the accumulated knowledge. The available mechanical studies are briefly reviewed, discussing factors such as age, sex, and the region of mechanical examination that may be responsible for the lack of unanimity in the reported findings. The rationale for acquiring layer-specific properties is presented along with the main results from our recent study. No mechanical vulnerability of ascending thoracic aortic aneurysms was evidenced in bicuspid aortic valve patients, corroborating present conservative guidelines concerning the management of bicuspid aortopathy. Weakening and additional vulnerability was evidenced in aged patients and those with coexisting valve pathology, aortic root dilatation, hypertension, and hyperlipidemia. Discussion of these results from age- and sex-matched subjects, accounting for the region- and layer-specific aortic heterogeneity, in relation to intact wall results and histologic confirmation, helps to reconcile previous findings and affords a universal interpretation of ascending aorta mechanics in bicuspid aortopathy.

scholarly journals Phenotypic and Functional Changes of Endothelial and Smooth Muscle Cells in Thoracic Aortic Aneurysms

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Malashicheva ◽  
Daria Kostina ◽  
Aleksandra Kostina ◽  
Olga Irtyuga ◽  
Irina Voronkina ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Aortic Valve ◽  
Smooth Muscle Cells ◽  
Aortic Wall ◽  
Muscle Cells ◽  
Aortic Aneurysms ◽  
Cell Phenotype ◽  
Functional Markers ◽  
Thoracic Aortic Aneurysms

Thoracic aortic aneurysm develops as a result of complex series of events that alter the cellular structure and the composition of the extracellular matrix of the aortic wall. The purpose of the present work was to study the cellular functions of endothelial and smooth muscle cells from the patients with aneurysms of the thoracic aorta. We studied endothelial and smooth muscle cells from aneurysms in patients with bicuspid aortic valve and with tricuspid aortic valve. The expression of key markers of endothelial (CD31, vWF, and VE-cadherin) and smooth muscle (SMA, SM22α, calponin, and vimentin) cells as well extracellular matrix and MMP activity was studied as well as and apoptosis and cell proliferation. Expression of functional markers of endothelial and smooth muscle cells was reduced in patient cells. Cellular proliferation, migration, and synthesis of extracellular matrix proteins are attenuated in the cells of the patients. We show for the first time that aortic endothelial cell phenotype is changed in the thoracic aortic aneurysms compared to normal aortic wall. In conclusion both endothelial and smooth muscle cells from aneurysms of the ascending aorta have downregulated specific cellular markers and altered functional properties, such as growth rate, apoptosis induction, and extracellular matrix synthesis.

scholarly journals The Pathophysiological Significance of Fibulin-3

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1294
Author(s):  
Imogen Livingstone ◽  
Vladimir N. Uversky ◽  
Dominic Furniss ◽  
Akira Wiberg
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Structural Integrity ◽  
Association Studies ◽  
Retinal Dystrophy ◽  
Elastic Fibre ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Extracellular Matrix Protein ◽  
Genome Wide Association Studies ◽  
Research Fields

Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular degeneration called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD). EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, EFEMP1 expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.

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