Gene expression in aortic aneurysms associated with tricuspid and bicuspid valves
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE5180 | GEO | 2007/06/28
SECONDARY ACCESSION(S): PRJNA96599
REPOSITORIES: GEO
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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: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:The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAV) and tricuspid valves with (TAVc) and without (TAVn) aortic valve stenosis. Ten human BAV and nine TAVc were collected from male who underwent primary aortic valve replacement. Eight TAVn were obtained from male who underwent heart transplantation. mRNA levels were measured using Illumina HumanHT-12 v4 Expression BeadChip and compared between valve groups.
2016-09-22 | GSE83453 | 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.
2011-06-24 | GSE30197 | GEO
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:Purpose: The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve (BAV) are unknown. The objective of this study was to identify genes differentially expressed between calcified BAV and tricuspid valves with (TAVc) and without (TAVn) calcification using RNA sequencing (RNA-Seq). Methods: Ten human calcified BAV and nine TAVc were collected from men who underwent aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured using the Illumina HiSeq 2000 system. Reads were aligned with TopHat. Cuffdiff, DESeq, edgeR, and SAMSeq were used to compare gene expression. Genes with adjusted P < 0.05 in the four methods were called differentially expressed. Pathway analysis was performed with IPA. Results: Two genes were up-regulated and none were down-regulated in BAV compared to TAVc. There were 462 genes up-regulated and 282 down-regulated in BAV compared to TAVn. Compared to TAVn, 329 genes were up- and 170 were down-regulated in TAVc. Conclusions: This is the first transcriptome study on calcified and normal aortic valves using RNA-Seq. BAV and TAVc have a highly similar expression profile. These results contribute to our molecular understanding of AS and the identification of new therapeutic targets that are urgently needed to prevent, slow the development or treat AS in patients with bicuspid and tricuspid valves.
2016-09-22 | GSE76717 | GEO
Project description:Purpose: The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve (BAV) are unknown. The objective of this study was to identify genes differentially expressed between calcified BAV and tricuspid valves with (TAVc) and without (TAVn) calcification using RNA sequencing (RNA-Seq). Methods: Ten human calcified BAV and nine TAVc were collected from men who underwent aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured using the Illumina HiSeq 2000 system. Reads were aligned with TopHat. Cuffdiff, DESeq, edgeR, and SAMSeq were used to compare gene expression. Genes with adjusted P < 0.05 in the four methods were called differentially expressed. Pathway analysis was performed with IPA. Results: Two genes were up-regulated and none were down-regulated in BAV compared to TAVc. There were 462 genes up-regulated and 282 down-regulated in BAV compared to TAVn. Compared to TAVn, 329 genes were up- and 170 were down-regulated in TAVc. Conclusions: This is the first transcriptome study on calcified and normal aortic valves using RNA-Seq. BAV and TAVc have a highly similar expression profile. These results contribute to our molecular understanding of AS and the identification of new therapeutic targets that are urgently needed to prevent, slow the development or treat AS in patients with bicuspid and tricuspid valves.
2016-09-22 | GSE76712 | 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: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: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.
2016-01-15 | GSE26155 | GEO