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 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.

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.

The Value of Circulating Biomarkers in Bicuspid Aortic Valve-Associated Aortopathy

2016 ◽  
Vol 66 (04) ◽  
pp. 278-286 ◽  
Author(s):  
Shiho Naito ◽  
Mathias Hillebrand ◽  
Alexander Bernhardt ◽  
Annika Jagodzinski ◽  
Lenard Conradi ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Risk Stratification ◽  
Bicuspid Aortic Valve ◽  
Aortic Aneurysms ◽  
Conventional Imaging ◽  
Circulating Biomarkers ◽  
Screening Process ◽  
Cross Sectional ◽  
Thoracic Aortic Aneurysms ◽  
Definition Of

AbstractTraditional risk stratification model of bicuspid aortic valve (BAV) aortopathy is based on measurement of maximal cross-sectional aortic diameter, definition of proximal aortic shape, and aortic stiffness/elasticity parameters. However, conventional imaging-based criteria are unable to provide reliable information regarding the risk stratification in BAV aortopathy, especially considering the heterogeneous nature of BAV disease. Given those limitations of conventional imaging, there is a growing clinical interest to use circulating biomarkers in the screening process for thoracic aortic aneurysms as well as in the risk-assessment algorithms. We aimed to systematically review currently available biomarkers, which may be of value to predict the natural evolution of aortopathy in individuals with BAV.

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 Marfan Syndrome, A Review

2018 ◽  
Vol 4 (2) ◽  
pp. 33
Author(s):  
Gerard Pals
Keyword(s):  
Marfan Syndrome ◽  
Index Finger ◽  
The Body ◽  
Aortic Aneurysms ◽  
Tall Stature ◽  
Aortic Dilatation ◽  
Thoracic Aortic Aneurysms ◽  
Ocular Symptoms ◽  
Arm Span ◽  
Lens Luxation

Marfan syndrome is named after the French pediatrician Antoine Bernard-Jean Marfan who described in 1896 a girl with arachnodactyly and long limbs1. The patient also had congenital contractures of the elbows and would not fulfill the current criteria for Marfan syndrome. She probably was suffering from a condition that we now call contractural arachnodactyly, caused by mutations in the FBN2 gene.The clinical features of Marfan syndrome affect many systems of the body. The most obvious are the skeletal features, long limbs, tall stature, long thin fingers (arachnodactyly or spider fingers). The skeletal features can be scored objectively as: arm span more than 1.05 x body length; wrist sign (thumb and index finger can encircle the wrist of the other hand with at least one digit overlap) and thumb sign (when making a fist around the thumb, one digit of the thumb sticks out). The main neurological symptom is dural ectasias. The most severe symptoms are cardiovascular: mitralis valve prolapse, aortic dilatation and thoracic aortic aneurysms and dissections, which may lead to sudden death5. However, I noticed in discussions with patients that they often consider the ocular symptoms, severe myopia and lens luxation, the worst for themselves, because the latter may lead to blindness.

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 Downregulation of the Yes-Associated Protein Is Associated with Extracellular Matrix Disorders in Ascending Aortic Aneurysms

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Haiyang Li ◽  
Wenjian Jiang ◽  
Weihong Ren ◽  
Dong Guo ◽  
Jialong Guo ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Aortic Wall ◽  
Critical Role ◽  
Aortic Aneurysms ◽  
Clinical Samples ◽  
Elastic Fibers ◽  
Cardiovascular Development ◽  
The Media ◽  
And Function ◽  
First Time

Previous studies indicate that extracellular matrix (ECM) disorders lead to the apoptosis of Vascular Smooth Muscle Cells (VSMCs), which impairs the aortic wall by reducing the generation of elastic fibers, and ultimately result in ascending aortic aneurysm. The critical role of the Yes-associated protein (YAP) has been elucidated in cardiac/SMC proliferation during cardiovascular development. However, the association of YAP expression and extracellular matrix disorders in ascending aortic aneurysms is not clear. Here, we present for the first time that the downregulation of YAP in VSMCs is associated with ECM disorders of the media in ascending aortic aneurysms. We found that aortic ECM deteriorated with increased apoptotic VSMCs. Moreover, expression of YAP was dramatically reduced in the aortic walls of patients with ascending aortic aneurysms, while the normal aortic samples exhibited abundant YAP in the VSMCs. These results suggest that downregulation of YAP leads to apoptosis of VSMCs, which are essential for the homeostasis of the aortic wall. The resultant ECM disorders affect aortic structure and function and contribute to the development of ascending aortic aneurysms. In summary, through assessment of clinical samples, we revealed the association between downregulation of YAP in VSMCs and the development of ascending aortic aneurysms, providing new insight into the pathogenesis of this disease.

Association of C-Reactive Protein-to-Albumin Ratio With the Presence and Progression of Abdominal Aortic Aneurysm

Angiology ◽  
2020 ◽  
pp. 000331972095408
Author(s):  
Sinan Cerşit ◽  
Lutfi Öcal ◽  
Muhammed Keskin ◽  
Mustafa Ozan Gürsoy ◽  
Macit Kalçik ◽  
...  
Keyword(s):  
Multivariate Logistic Regression Analysis ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
C Reactive Protein ◽  
Cross Sectional ◽  
Albumin Ratio ◽  
Inflammatory Biomarker ◽  
Reactive Protein ◽  
Abdominal Aortic ◽  
Normal Controls

Aortic dilatation due to inflammation may lead to an increase in C-reactive protein (CRP) levels. We investigated the possible relationship between CRP-to-albumin ratio (CAR) and presence and progression of abdominal aortic aneurysms (AAAs). The study included 150 patients previously diagnosed with AAA (diameter 40-54 mm) and 100 normal controls. Clinical and laboratory parameters and maximal cross-sectional AAA diameters (measured by computed tomography angiography) were obtained from all participants at baseline assessment as well as after 1 year for those with an AAA. The patients with AAA had significantly higher serum CAR compared with controls at baseline (P < .001). Increased serum CAR was found to be an independent predictor of the presence of AAA (odds ratio: 3.162, 95% CI: 1.690-5.126, P = .001) after multivariate logistic regression analysis. There was a significant increase in aortic diameter and CAR after 1 year in the patients with AAA ( P < .001; P = .003); a significant correlation was found between changes in the diameter of AAAs and CAR ( r = 0.414; P = .005). Serum CAR may be useful as an inflammatory biomarker for the presence and progression of AAA.

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