Genetic Variation Associated with Bicuspid Aortic Valve in Turner Syndrome
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PROVIDER: PRJNA432473 | ENA |
REPOSITORIES: ENA
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Project description:Genetic Variation Associated with Bicuspid Aortic Valve in Turner Syndrome
| PRJNA432472 | ENA
Project description:<p>Turner syndrome is a disorder affecting only girls and women, which is caused by a complete or partial loss of the second sex chromosome. Girls and women with Turner syndrome have a variety of phenotypes. Of interest to this study is aortopathy, including bicuspid aortic valve (BAV) and thoracic aortic dilation (TAD) in which we know that 25 - 50% of girls with Turner syndrome are born with.</p> <p>The aorta is the main artery that conducts the blood out of the heart. The aortic valve guards the entrance to the aorta. When the aortic valve has two leaflets instead of the usual three it is called a BAV. BAV is more common than all other congenital heart defects combined. BAV commonly causes obstructions to blood flow out of the heart or become leaky over time. BAV often occurs in combination with TAD. In Turner syndrome, TADs are increased 50-100 fold compared to the general population. Currently, there are no effective approaches or pre-surgical treatments for aortic disease. Therefore, progression of aortic disease in individuals with BAV/TAD can result in catastrophic aortic dissection, rupture, and death. </p> <p>Our goal is to leverage DNA sequencing and carefully curated patient samples to gain a better understanding of the molecular mechanisms that cause these inter-related aortic diseases. </p>
| phs001531 | dbGaP
Project description:Bicuspid aortic valve is well known as a risk factor of dilation of ascending aorta. But the mechanisms of dialation are unknown. Morever, patients with bicuspid aortic valve tend to be aortic valve disease at younger age. After aortic valve surgery, if ascending aorta is dilated, the patient must be performed re-operation. For that reason, surgery for aortic root or ascending aorta is recommended to patient with bicuspid aortic valve with dilated ascending aorta. We thought that abnormality of cell cycle of the structure protein participated in ascending aorta dilation of patient with bicuspid aortic valve. We resected the wall of the ascending aota from patient undergoing aortic valve replacement for aortic valve stenosis during operation, and performed immunohistochemical staining for akt. Anti Akt antibodys were stained much on aortic media with bicuspoed aortic valve. Akt is a protein that is involved in mTOR / PI3K, and modulate the cell differenciation and proliferation. Further, the same samples were analyzed using a microarray method. On bicuspid aortic valve patients, the expression of TSC2 is reduced, and GβL is increased. TSC2 inhibit this pathway, and MLST8 activate this pathway. In the ascending aorta of BAV patients, PI3K / mTOR system is considered to be activated. When this pathway is activated, cell proliferation and cytodifferentiation are promoted abnormally,
2017-06-30 | GSE83675 | GEO
Project description:Genome wide DNA methylation profiling of ascending aorta tissue samples from normal, aortic dissection and bicuspid aortic valve patients with aortic dilation. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across more than 450,000 CpGs in ascending aorta samples. Samples included 6 normal donors, 12 patients with aortic dissection and 6 patients with bicuspid aortic valve and dilated aorta.
2019-07-11 | GSE84274 | GEO
Project description:Bicuspid aortic valve (BAV) is a common congenital cardiac anomaly, with an estimated incidence of 1-2%. It is responsible for the greatest burden of aortic valve disease in patients younger than 70 years in North America. We performed microRNA profiling in end-stage valve leaflets with BAV and TAV. Patients undergoing elective aortic valve replacement for aortic stenosis at St. Michael’s Hospital, University of Toronto, between June 2010 and June 2011 were enrolled. Aortic valve leaflets were obtained intraoperatively from patients with congenital bicuspid (BAV; N=10) and tricuspid aortic valves (TAV; N=10) at the time of valve replacement. Leaflets were flash frozen in liquid nitrogen. MiRNA was isolated using the miRNeasy kit (Qiagen, Hilden, Germany) according to the manufacturer`s instructions. For miRNA microarray analysis, total RNA was directly labeled with biotin and hybridized to the GenoExplorer microRNA human array containing 1583 human miRNA probes (Genosensor, Tempe, AZ) and the fluorescent signals were then scanned using a GenePix 4000b Biochip. The average of 3 mean fluorescence signal intensities for each miRNA probe was normalized to that for tRNAmet. Precursor miRNAs detected at 2-fold greater than background were considered to be expressed. Data were analyzed with GenePix 5.0 software, provided by GenoSensor Corp.
2011-06-24 | E-GEOD-30197 | biostudies-arrayexpress
Project description:Bicuspid aortic valve (BAV) is a common congenital cardiac anomaly, with an estimated incidence of 1-2%. It is responsible for the greatest burden of aortic valve disease in patients younger than 70 years in North America. We performed microRNA profiling in end-stage valve leaflets with BAV and TAV.
2011-06-24 | GSE30197 | GEO
Project description:and with higher incidence if associated to bicuspid aortic valve (BAV) for unknown reasons. TAA is usually diagnosed fortuitously and the lack of effective drug therapy to delay progression and avoid dissection lies in the limited knowledge of pathophysiology. Objectives. We aimed to identify the molecular hallmarks that difference the aortic dilatation associated to bicuspid (BAV) and tricuspid aortic valve (TAV) patients while setting plasma diagnostic molecular panels valve-associated. Methods. Sporadic TAA patients and control subjects (n=91) were classified according to valve type (BAV, TAV). Vascular smooth muscle cells isolated from TAA patients’ aortas were firstly analyzed by mass spectrometry based high-throughput proteomics according to valve type. Extracellularly secreted proteins were secondly analyzed in plasma from TAA patients versus control subjects as diagnostic candidates. Results. Aneurysmal aortas from BAV patients showed a stress phenotype, weakened extracellular matrix interactions, DNA damage and affected protein homeostasis compared to TAV patients. Two plasma marker panels of sporadic TAA valveassociated were identified, showing significant correlation with aortic diameter for C1QTNF5, LAMA2, and SPARC proteins, in BAV patients, and for CP and FAP proteins, in TAV patients. Conclusions. The arterial wall of BAV patients shows a limited capacity to counteract drivers of sporadic TAA while resembling aged arteries.The molecular pathways identified here support the need of differential molecular diagnosis and therapeutic approaches for BAV and TAV patients.
2024-10-17 | PXD043062 | Pride
Project description:The molecular basis of aortic valve degeneration (AVD) is unclear. The extracellular matrix (ECM) of the valve is in dynamic reciprocity with its surrounding microenvironment and contains molecular traits of the pathophysiological processes. We compared abundances of ECM proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV) by employing a new method for protein preparation and quantitative mass-spectrometry analysis.
2023-09-03 | PXD025002 | Pride
Project description:Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA. Experiment Overall Design: Aneurysmal tissue of ascending aorta was collected from 13 patients with bicuspid aortic valve (BAV) and 12 patients with tricuspid aortic valve (TAV). Patients were selected on the basis of aortic diameter, age and other disease conditions. Patients with giant cell aortitis, cardiovascular abnormalities, inherited connective tissue disorders such as Marfan and Ehlers-Danlos syndrome were excluded from the study. RNA was extracted using Invitrogen RNA extraction kit and shown to be of adequate quality before application to Affymetrix microarray U133A gene chips probing for over 16,000 genes per chip. Two different methods of data analysis were performed: a linear model and GeneSpring.
2009-02-07 | E-GEOD-5180 | biostudies-arrayexpress
Project description:Patients with bicuspid aortic valve (BAV) have increased risk of thoracic ascending aortic aneurysm (AscAA) and dissection compared to those with a normal tricuspid aortic valve (TAV). The present study was undertaken to evaluate whether differences in gene expression exist in aortas from BAV and TAV patients with AscAA. Keywords: disease state analysis
2007-06-28 | GSE5180 | GEO