Plasma biomarkers for aortic dilation in BAV patients
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Blood Plasma
SUBMITTER: 
Zhang Weijia
LAB HEAD: Weijia Zhang
PROVIDER: PXD027125 | Pride | 2021-08-19
REPOSITORIES: Pride
Dataset's files
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Project description:BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients. METHODS AND RESULTS: Tissue biopsies for RNA and histological analyses were obtained from aorta of non-dilated (<40mm) and dilated (>45mm) aorta of BAV and TAV patients (in total 131 patients). Additional controls were from mammary artery of the same patients (n=88) and aorta from transplant donors (n=13). Gene expression profiles generated using Affymetrix Exon arrays were analyzed from controls and from aorta intima-media and adventitia of patients (in total 345 samples). 606 genes in aortic intima-media were found to be differentially expressed with dilation. Of these, only few (<4%) were differentially expressed in both BAV and TAV patients. Gene set enrichment analysis identified cell adhesion and extracellular region gene ontology sets as common features of TAA in BAV and TAV patients. The set of immune response genes was observed to be particularly overexpressed in aortic media of dilated TAV samples. CONCLUSION: The divergent gene expression profiles indicate fundamental differences in TAA etiology of BAV and TAV patients. Immune response activation solely in the aorta media of TAV patients suggests that inflammation is a causal factor of TAA in this patient group. Biobank of patient material. Each tissue sample is from a different patient as indicated by patient ID.
2016-01-15 | E-GEOD-26155 | biostudies-arrayexpress
Project description:Conducted proteomics on samples from patients with aortic aneurysm and from non-dilated controls. Furthermore, we investigated both patients with bicuspid aortic valves (BAV) and also the more normal tricuspid aortic valves (TAV). The aim was to elucidate the molecular mechanisms behind the higher propensity of BAV patients to develop aorta dilation and consequent aortic aneurysm.
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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
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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:BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients. METHODS AND RESULTS: Tissue biopsies for RNA and histological analyses were obtained from aorta of non-dilated (<40mm) and dilated (>45mm) aorta of BAV and TAV patients (in total 131 patients). Additional controls were from mammary artery of the same patients (n=88) and aorta from transplant donors (n=13). Gene expression profiles generated using Affymetrix Exon arrays were analyzed from controls and from aorta intima-media and adventitia of patients (in total 345 samples). 606 genes in aortic intima-media were found to be differentially expressed with dilation. Of these, only few (<4%) were differentially expressed in both BAV and TAV patients. Gene set enrichment analysis identified cell adhesion and extracellular region gene ontology sets as common features of TAA in BAV and TAV patients. The set of immune response genes was observed to be particularly overexpressed in aortic media of dilated TAV samples. CONCLUSION: The divergent gene expression profiles indicate fundamental differences in TAA etiology of BAV and TAV patients. Immune response activation solely in the aorta media of TAV patients suggests that inflammation is a causal factor of TAA in this patient group.
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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>
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Project description:Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. In this study, protein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. To verify it, we constructed aorta-on-a-chip to replicate the rhythmic tensile on human aorta, on which human aortic smooth muscle cells (HAoSMCs) endured a microenvironment of biomimetic strain unattainable in animal models. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) rescued the mitochondrial dysfunction in HAoSMCs from BAV-TAA patients. These findings suggest that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA.
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