Gene expression profile of normal and calcified stenotic human aortic valves
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-DIXA-D-1010 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The molecular mechanisms leading to premature development of aortic valve stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The objective of this study was to identify genes differentially expressed between calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn were obtained from men who underwent heart transplantation. mRNA levels were measured by RNA-Seq and compared between valve groups. Two genes were upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a similar gene expression response to AS in individuals with bicuspid and tricuspid valves. There were 462 genes upregulated and 282 downregulated in BAVc compared with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were downregulated. A total of 273 upregulated and 147 downregulated genes were concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56 and 84% of significant genes in the first and second comparisons, respectively. This indicates that extra genes and pathways were altered in BAVc. Shared pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were also more extensively altered in BAVc. The top pathway enriched for genes differentially expressed in calcified compared with normal valves was fibrosis, which support the remodeling process as a therapeutic target. These findings are relevant to understand the molecular basis of AS in patients with bicuspid and tricuspid valves.
| S-EPMC6195654 | biostudies-literature
Project description:We explored gene expression profile of human aortic valves in patients with or without aortic stenosis. The dataset that we generated constitutes a large-scale quantitative measurements of gene expression in normal and stenotic human valves. The goal was to compare gene expression levels between the two groups and identified a list of genes that are up- or down-regulated in aortic stenosis. Keywords: disease state analysis
2009-07-09 | GSE12644 | GEO
Project description:We explored gene expression profile of human aortic valves in patients with or without aortic stenosis. The dataset that we generated constitutes a large-scale quantitative measurements of gene expression in normal and stenotic human valves. The goal was to compare gene expression levels between the two groups and identified a list of genes that are up- or down-regulated in aortic stenosis. Keywords: disease state analysis Gene expression was performed on ten normal and ten aortic stenosis valves
2009-07-09 | E-GEOD-12644 | 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:Valve interstial cells(VICs) are the major cellular compents in the aortic valve. Under pathological circumstances, normal VICs differentiate into myofibroblasts or osteoblast-like phentotypes, which play important roles in the pathogenesis of calcified aortic valve disease. We used micrroarrary analysis to compare the global programme of gene expression in normal and calcified human aortic valve intersitial cells (VICs), in order to find out some key factors that mediate the phenotype change of VICs.
2016-10-23 | GSE88803 | GEO
Project description:Purpose: Calcific aortic valve stenosis (AS) is a fatal disease with currently no medical therapy. Some genes were associated with AS, but the genetic architecture of the disease has yet to be discovered. The objective of this study was to combine genome-wide association studies (GWAS) and gene expression in human valve tissues to identify new susceptibility genes of AS. Methods: A meta-analysis was performed combining the results of two independent GWAS in 474 patients that underwent aortic valve replacement from Quebec city and 486 echocardiography cases from France. The controls consisted of 3,151 publically available individuals of European ancestry. Sixty-nine SNPs selected from the meta-analysis (p < 1 x 10-4) were followed-up for replication in a third cohort of 395 cases and 404 controls. Single marker and gene set association analyses were performed. The mRNA expression levels of susceptibility genes were evaluated in 19 human aortic valves with (n=9) and without (n=10) AS by RNA sequencing. Results: Single marker analysis identified 15 SNPs with p values lower than 1 x 10-6 in the meta-analysis near the FAR2 gene on chromosome 12. At the replication stage, none of these SNPs were confirmed and three other SNPs on chromosomes 2 and 5 reached p < 0.05. Gene set analysis revealed more meaningful association with the calcium signaling pathway enriched for genes mapped to disease-associated SNPs. Genes in this pathway including F2R, GNA14, HTR4, P2RX6, and TNNC1 were found differentially expressed in valves with and without AS. Conclusions: This integrative genomic study identified new AS susceptibility genes expressed in human valve tissue. Moderate but coordinated genetic association and expression patterns were observed for genes implicated in the calcium signaling pathway and may provide new therapeutic targets to treat this frequent and rising life-threatening disease.
2015-12-09 | GSE55492 | GEO
Project description:Purpose: Calcific aortic valve stenosis (AS) is a fatal disease with currently no medical therapy. Some genes were associated with AS, but the genetic architecture of the disease has yet to be discovered. The objective of this study was to combine genome-wide association studies (GWAS) and gene expression in human valve tissues to identify new susceptibility genes of AS. Methods: A meta-analysis was performed combining the results of two independent GWAS in 474 patients that underwent aortic valve replacement from Quebec city and 486 echocardiography cases from France. The controls consisted of 3,151 publically available individuals of European ancestry. Sixty-nine SNPs selected from the meta-analysis (p < 1 x 10-4) were followed-up for replication in a third cohort of 395 cases and 404 controls. Single marker and gene set association analyses were performed. The mRNA expression levels of susceptibility genes were evaluated in 19 human aortic valves with (n=9) and without (n=10) AS by RNA sequencing. Results: Single marker analysis identified 15 SNPs with p values lower than 1 x 10-6 in the meta-analysis near the FAR2 gene on chromosome 12. At the replication stage, none of these SNPs were confirmed and three other SNPs on chromosomes 2 and 5 reached p < 0.05. Gene set analysis revealed more meaningful association with the calcium signaling pathway enriched for genes mapped to disease-associated SNPs. Genes in this pathway including F2R, GNA14, HTR4, P2RX6, and TNNC1 were found differentially expressed in valves with and without AS. Conclusions: This integrative genomic study identified new AS susceptibility genes expressed in human valve tissue. Moderate but coordinated genetic association and expression patterns were observed for genes implicated in the calcium signaling pathway and may provide new therapeutic targets to treat this frequent and rising life-threatening disease. Samples of aortic valves were collected from 19 male patients undergoing aortic valve replacement surgery. RNA sequencing was performed using the Illumina Hiseq 2000. Three pairwise comparison among the two kind of valves were made.
2015-12-09 | E-GEOD-55492 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-09-22 | GSE76718 | 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 | 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