Project description:Aortic valves are collected from patients with severe aortic valve stenosis undergoing aortic valve replacement at the Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), Quebec City, Canada. From this biobank collection, transcriptomic analyses from 240 aortic valves were performed. All valves were tricuspid and had a fibro-calcific remodeling score of 3 or 4. RNA was extracted from valve leaflets and gene expression evaluated using the Illumina HumanHT-12 v4 Expression BeadChip. The main objective of this study was to perform a large-scale expression quantitative trait loci (eQTL) mapping study on human aortic valves.
Project description:Calcified aortic valve leaflets (CAVs) were explanted from patients with severe aortic valve stenosis undergoing aortic valve replacement at the Department of Cardiovascular Surgery, Union Hospital, affiliated to Tongji Medical College. Control non-calcified aortic valves with normal echocardiographic analyses were obtained during heart transplant procedures. RNA was extracted from valve leaflets and gene expression evaluated using the Arraystar Human mRNA Array. This study aimed to perform the expression analysis of mRNA on human aortic valves.
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
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
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.
Project description:Several microRNAs (miRNAs) have been identified to play crucial roles in calcificated aortic valves disease, numerous miRNAs are still waiting to be explored. In this study, we compared the miRNA expression profiles of human non-calcified (n=3) and calcified (n=5) aortic valves, and found that compared with the normal control valves, 152 miRNAs were up-regulated and 186 miRNAs were down-regulated in calcified aortic valves. Among the top hit down-regulated miRNAs, we found that the expression level of miR-139-5p was negatively correlated with the osteogenic genes RUNX2 and BMP3, and was also down-regulated during the osteogenic differentiation of primary human aortic VICs.
Project description:We explored the hypothesis that Serotonin (5HT) receptor signaling, that can be enhanced with 5HT transporter blockade with Fluoxetine (Fluox), in the aortic valve may vary based upon the biomechanical activity of the aortic valve leaflet. We used Affymetrix microarrays to study gene expression profiling of Porcine Aortic Valves (PAV) incubated under organ culture conditions for 24 hours in either a static state or with 10% cyclic stretch, simulating physiologic leaflet motion. PAV in the bioreactor with or without stretch were exposed to 5HT along or the combination 5HT plus Fluox. Fresh porcine aortic valves were obtained from a local abattoir. The three leaflets were excised from each valve and a rectangular section of tissue 15x10 mm was isolated from the central region of each valve cusp. These samples were randomized and assigned to one of four groups. The experimental groups were: 1) Static conditions with no agents added; 2) Cyclic stretch conditions with no agents added; 3) Static conditions with 5HT plus Fluox added; and 4) Cyclic stretch conditions with 5HT plus Fluox added.
Project description:We explored the hypothesis that Serotonin (5HT) receptor signaling, that can be enhanced with 5HT transporter blockade with Fluoxetine (Fluox), in the aortic valve may vary based upon the biomechanical activity of the aortic valve leaflet. We used Affymetrix microarrays to study gene expression profiling of Porcine Aortic Valves (PAV) incubated under organ culture conditions for 24 hours in either a static state or with 10% cyclic stretch, simulating physiologic leaflet motion. PAV in the bioreactor with or without stretch were exposed to 5HT along or the combination 5HT plus Fluox.
Project description:We performed single cell RNA sequencing (scRNA-seq) for 6,574 cells from the aortic valves of C57BL/6J (wild type), Ldlr-/-, and Apoe-/- mice. The extensive single cell profiles depicted hyperlipidemia-associated cellular dynamics in aortic valves.
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.