Search results for " thoracic aortic aneurysm"
showing 10 items of 24 documents
Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms
2019
AbstractAneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMC…
Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus
2006
We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection ( TAAD) and patent ductus arteriosus (PDA)(1,2) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocal…
Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm
2019
This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve.A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal compo…
Comparison of hemodynamic and structural indices of ascending thoracic aortic aneurysm as predicted by 2-way FSI, CFD rigid wall simulation and patie…
2018
Patient-specific computational modeling is increasingly being used to predict structural and hemodynamic parameters, especially when current clinical tools are not accessible. Indeed, pathophysiology of ascending thoracic aortic aneurysm (ATAA) has been simulated to quantify the risk of complications by novel prognostic parameters and thus to improve the clinical decision-making process related to the intervention of ATAAs. In this study, the relevance of aneurysmal wall elasticity in determining parameters of clinical importance, such as the wall shear stress (WSS), is discussed together with the significance of applying realistic boundary conditions to consider the aortic stretch and twis…
Focus on the unique mechanisms involved in thoracic aortic aneurysm formation in bicuspid aortic valve versus tricuspid aortic valve patients: clinic…
2013
OBJECTIVES: The involvement of different factors in the onset of thoracic aortic aneurysm (TAA) in patients with a bicuspid aortic valve (BAV) vs those with a tricuspid aortic valve (TAV) is well recognized. However, the molecular, genetic and cellular mechanisms driving TAA remain unclear. The aim of this study was to identify the different mechanisms involved in TAA development in patients with BAV vs TAV. METHODS: Aorta specimens and DNA samples were collected from 24 BAV (18 men and 6 women; mean age: 54.2 ± 14.39 years) and 110 TAV (79 men and 31 women, mean age: 66 ± 9.8 years) patients. A control group of 128 subjects (61 men and 67 woman, mean age: 61.1 ± 5.8 years) was also enrolle…
Difference in hemodynamic and wall stress of ascending thoracic aortic aneurysms with bicuspid and tricuspid aortic valve.
2012
The aortic dissection (AoD) of an ascending thoracic aortic aneurysm (ATAA) initiates when the hemodynamic loads exerted on the aneurysmal wall overcome the adhesive forces holding the elastic layers together. Parallel coupled, two-way fluid–structure interaction (FSI) analyses were performed on patient-specific ATAAs obtained from patients with either bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) to evaluate hemodynamic predictors and wall stresses imparting aneurysm enlargement and AoD. Results showed a left-handed circumferential flow with slower-moving helical pattern in the aneurysm's center for BAV ATAAs whereas a slight deviation of the blood flow toward the anterolater…
On the severity of aortic stenosis in ascending aortic aneurysm: A computational tool to examine ventricular-arterial interaction and aortic wall str…
2020
Abstract An ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular consequence of vessel dilatation that portends adverse events and death. From a clinical perspective, ATAA should not be treated as an isolated disease, and surgery is often carried out in the presence of AS, aortic insufficiency or a calcified valve leaflet. Aortic stenosis (AS) is common in ATAAs and leads to both vessel rigidity and left ventricular (LV) impairment. In this study, lumped-parameter modeling and computational analysis were used to assess the change in the wall shear stress (WSS) and intramural wall stress of patient-specific ATAA models with different degrees of AS (i.e., mild to sev…
Regional variation of wall shear stress in ascending thoracic aortic aneurysms.
2014
The development of an ascending thoracic aortic aneurysm is likely caused by excessive hemodynamic loads exerted on the aneurysmal wall. Computational fluid-dynamic analyses were performed on patient-specific ascending thoracic aortic aneurysms obtained from patients with either bicuspid aortic valve or tricuspid aortic valve to evaluate hemodynamic and wall shear parameters, imparting aneurysm enlargement. Results showed an accelerated flow along the outer aortic wall with helical flow in the aneurysm center for bicuspid aortic valve ascending thoracic aortic aneurysms. In a different way, tricuspid aortic valve ascending thoracic aortic aneurysms exhibited normal systolic flow without su…
Dissection and 3D reconstruction of healthy and aneurysmal human ascending thoracic aorta
2010
Ascending thoracic aortic aneurysm (ATAA) is among the most devastating forms of cardiovascular disease, causing a significant mortality despite current medical and surgical treatments [1]. This form of disease is a predisposing factor for spontaneous aortic dissection which in general results in the initiation of an intimal flap and its propagation due to blood flow. Since aortic dissection fails by separation of the elastic layers [2], the delamination strength of ATAA tissues was investigated by designing and performing mechanical tests that simulate the in-vivo tearing condition of the aortic wall. Specifically, the delamination tests were carried out on nonaneurysmal and aneurysmal hum…
Fiber Micro-Architecture in the Longitudinal-Radial and Circumferential-Radial Planes of Ascending Thoracic Aortic Aneurysm Media.
2013
It was recently demonstrated by our group that the delamination strength of ascending thoracic aortic aneurysms (ATAA) was lower than that of control (CTRL, non-aneurysmal) ascending thoracic aorta (ATA), and the reduced strength was more pronounced among bicuspid (BAV) vs. tricuspid aortic valve (TAV) patients, suggesting a different risk of aortic dissection for BAV patients. We hypothesized that aortic valve morphologic phenotype predicts fiber micro-architectural anomalies in ATA. To test the hypothesis, we characterized the micro-architecture in the longitudinal-radial (Z-RAD) and circumferential-radial (Θ-RAD) planes of human ATA tissue that was artificially dissected medially. The ou…