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: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: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:Purpose: The goal of this study is to characterize the gene expression profiles and identify genes of interest (GOI) in stenotic (AS) and regurgitant (AI) human aortic valves using RNA sequencing technology. Methods: Aortic valve leaflets were collected from non-matched transplant donor hearts (NC) and from aortic valve replacement operations (AS or AI). Leaflets were washed in cold PBS, snap frozen, and stored at -80°C until RNA extraction. For each sample, total RNA was extracted, a cDNA library was generated, and an Illumina HiSeq 2500 was used to sequence each sample. 150-bp paired-ends reads were generated with approximately 30 million reads per sample. Sequencing was performed in duplicate for each sample. Paired-end clean reads were aligned to the reference genome using STAR. HTSeq v0.6.1 was used to count the read numbers mapped to each gene. Fragments per kilobases per million (FPKM) were calculated to estimate the level of gene expression. Differential gene expression analysis was performed using the DESeq2 R package. A model based on the negative binomial distribution was used to determine differential gene expression (log 2 [fold change]). P-values were adjusted using the Benjamini-Hochberg approach for controlling false discovery rate. Genes with adjusted P-values <0.05 found by DESeq2 were assigned as differentially-expressed genes (DEGs). Results: RNA sequencing analysis identified 8,621 DEGs among the AS, AI, and NC valves. Specifically, 6,438 genes were found to be differentially expressed between the AS and NC groups; 4,994 genes were found to be differentially expressed between the AI and NC groups; and 2,771 genes were found to be differentially expressed between the AS and AI groups. Of these, 1,979 (31%) genes were expressed at statistically different levels between the AS and NC groups, and 1,428 (29%) genes were expressed at statistically different levels between the AI and NC groups Conclusions: Overall, we have sequenced aortic leaflets from non-matched transplant donor hearts , thereby establishing a new standard for normal aortic valve transcriptional profiling. We have also sequenced human aortic valves with AI and demonstrated that valves with AI and AS possess unique gene expression patterns. The plethora of DEGs identified and our novel PPI networks for AS and AI have revealed new pathways missed by previous aortic valve studies. Our data lays the foundation for future gene editing studies and may guide researchers in developing novel therapeutic interventions for AS and AI.
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: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.