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Aortic Aneurysm iTRAQ HiRIEF proteomics

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Aorta, Aortic Endothelial Cell

DISEASE(S): Aortic Aneurysm

SUBMITTER: Rui Branca

LAB HEAD: Janne Lehtiö

PROVIDER: PXD003702 | Pride | 2016-12-23

REPOSITORIES: Pride

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			Action	DRS
	Sanela_2013apr23_pool1_100ug_IPG400-425_fr01.raw	Raw
	Sanela_2013apr23_pool1_100ug_IPG400-425_fr02.raw	Raw
	Sanela_2013apr23_pool1_100ug_IPG400-425_fr03.raw	Raw
	Sanela_2013apr23_pool1_100ug_IPG400-425_fr04.raw	Raw
	Sanela_2013apr23_pool1_100ug_IPG400-425_fr05.raw	Raw

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Publications

Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves.

Maleki Shohreh S Kjellqvist Sanela S Paloschi Valentina V Magné Joelle J Branca Rui Miguel Mamede RM Du Lei L Hultenby Kjell K Petrini Johan J Fuxe Jonas J Lehtiö Janne J Franco-Cereceda Anders A Eriksson Per P Björck Hanna M HM

Scientific reports 20161025

Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy ...[more]

PMID: 27779199

Similar Datasets

Aortic Aneurysm iTRAQ HiRIEF proteomics

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.

2017-03-31 | MSV000080837 | MassIVE

Transcription profiling of human patients with aortic aneurysms associated with tricuspid and bicuspid valves

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

Gene expression in aortic aneurysms associated with tricuspid and bicuspid valves

2007-06-28 | GSE5180 | GEO

Gene expression profile of calcified bicuspid, tricuspid and normal human aortic valves

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

RNA Expression Profile of Calcified Bicuspid, Tricuspid and Normal Human Aortic Valves by RNA Sequencing [TAV]

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

RNA Expression Profile of Calcified Bicuspid, Tricuspid and Normal Human Aortic Valves by RNA Sequencing [BAV]

2016-09-22 | GSE76712 | GEO

MiRNA microarray analysis of human bicuspid and tricuspid aortic valve leaflet tissues

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

The extracellular matrix landscape identifies different etiologies behind bicuspid and tricuspid aortic valve degeneration

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

Aorta-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease

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.

2021-09-11 | PXD026303 | Pride

Plasma biomarkers for aortic dilation in BAV patients

Project description:Bicuspid aortic valve (BAV) is the most common congenital heart anomaly and is prone to cause complications, such as valvular stenosis and thoracic aortic dilation. There is currently no reliable way to predict the progression rate to thoracic aortic aneurysm. Here, we aimed to characterize the proteomic landscape in the plasma of stenotic BAV patients and provide potential biomarkers to predict progressive aortic dilation. Plasma samples were obtained from 45 subjects (30 stenotic BAV patients and 15 healthy controls). All samples were properly prepared and analyzed using mass spectrometry (MS)-based label-free quantitative proteomics.

2021-08-19 | PXD027125 | Pride

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