ABSTRACT: In order to asses differences between expression profiles of postnatal and adult mice, RNA-sequencing was performed on RNA from postnatal day 2 and 4 month old murine aortic valves.
Project description:In order to analyze molecular changes in response to endothelial injury, the aortic valve in wild type mice was injured by inserting a thin anigoplasty guidewire into the mouse carotid artery and advancing the wire through the aortic valve opening. This procedure produced damage to the layer of valve endothelial cells surroung the outer edge of the valve leaflet. Sham surgery consisted of the same wire insertion prcoedure but the wire was not advanced to the level of the valve. The surgical procedure was performed in young (3-4 month old) and aging (16-18 month old) mice. Individual sham and injured aortic valves were collected 48 hours after surgery and submitted for sequencing (one valve per biological replicate).
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:RNA sequencing was performed to compare the transcriptome of aortic valves among 4 mouse models: fibulin-4 (Fbln4; EFEMP2 gene) knockout in endothelial cells (EC) using Tie2Cre (ECKO), Fbln4 knockout in smooth muscle cells (SMC) using SM22Cre (SMKO), EC and SMC Fbln4 double knockout (DKO), and Fbln4loxp/+ and Fbln4+/+ with SM22Cre and/or Tie2Cre used as CTRL. At 2 months old, DKO mice showed significantly thickening aortic valve leaflets than other mouse models. Therefore, this experiment was used to investigate the function of Fbln4 in aortic valve development and Fbln4 role in EC. RNAseq analysis indicates differences in gene expression in aortic valves of DKO mice compared to other models, that is enriched with EndMT process and fibrosis progression.
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 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: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 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 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.