Single nuclear gene expression profile of postnatal day 1 mouse aortic valve structures
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE269604 | GEO | 2025/01/08
REPOSITORIES: GEO
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Project description:We report transcriptional profiles of aortic valve tissue from calcific aortic valve disease (CAVD) and normal control (non-CAVD). We collected the aortic valve tissues from five patients with CAVD who underwent aortic valve replacement due to severe aortic valve stenosis. Aortic valve samples from patients with non-calcified aortic valve resection due to heart transplantation (recipient heart) or aortic dissection were collected as the control (non-CAVD). The inclusion criteria for CAVD group were as follows: 50-75 years old; undergoing aortic valve replacement due to severe AVS with significantly valvular calcification. The inclusion criteria for non-CAVD group were as follows: non-calcified aortic valve resection due to heart transplantation (recipient heart) or aortic dissection. For each sample, total RNA was extracted, a cDNA library was generated, and an Illumina NovaSeq 6000 was used to sequence each sample. Stringtie software was used to count the fragment within each gene, and TMM algorithm was used for normalization. Differential expression analysis was performed using R package edgeR. Differentially expressed RNAs with |log2(FC)| value >1, q value [false discovery rate (FDR) adjusted P-value] <0.05, and one group’s mean fragments per kilobase of exon per million reads mapped (FPKM) >1, were assigned as differentially-expressed genes (DEGs).
2023-06-28 | GSE235995 | GEO
Project description:Located at the junction of left ventricle and ascending aorta, aortic root is a central cardiovascular structure consisting of aortic valve and coronary ostium that are essential for systemic and coronary circulation, respectively. Malformations of aortic valve and coronary ostium are common birth defects and may occur together in human patients, leading to complex complications including aortic valve stenosis, myocardial ischemia, heart failure and sudden cardiac death. Despite of their physiological and clinical significances, the developmental and molecular mechanisms by which coordinate the formation of aortic valve and coronary ostium remain poorly understood. Here we report that SOX17 (SRY-box 17) is an essential transcription factor required for the maturation of aortic root, as well as the patterning of aortic valve and coronary ostium. We show in mouse that deletion of Sox17 in the aortic root endothelium results in defective aortic valve with underdeveloped non-coronary leaflet (NCL) or bicuspid aortic valve (BAV) without NCL. The valve defects are accompanied by misplaced left coronary ostium that reduces coronary blood flow, leading to myocardial hypoxia and death of embryos. Mechanistically, deletion of Sox17 decreases the expression of Pdgfb (Platelet derived growth factor, B polypeptide) in the aortic root endothelium and the PDGF growth signaling in the NCL mesenchyme and aortic root smooth muscle, both of which are derived from the second heart field (SHF) cardiomyocyte precursors. Furthermore, the deletion upregulates the expression of Ctgf (Connective tissue growth factor) and the extracellular matrix (ECM) genes, whereas downregulates the vascular smooth muscle genes, in the forming aortic root. Together, these findings support a developmental disease mechanism in which delayed growth and maturation of aortic root, due to lack of SOX17-PDGF/CTGF signaling, contributes to BAV and CAAs, two common congenital cardiovascular defects.
2022-04-09 | GSE129564 | GEO
Project description:Single nuclear gene expression profile of postnatal day 1 mouse aortic valve structures
| PRJNA1122639 | ENA
Project description:Calcific aortic valve disease (CAVD) is the most common valvular heart disease in the aging population, ranging from initial aortic valve sclerosis to advanced aortic valve stenosis (AVS), but its underlying mechanism remains poorly understood. The present study aimed to explore the differentially expressed long non-coding RNAs and genes in CAVD.
2023-05-31 | GSE233819 | GEO
Project description:Bicuspid aortic valve is well known as a risk factor of dilation of ascending aorta. But the mechanisms of dialation are unknown. Morever, patients with bicuspid aortic valve tend to be aortic valve disease at younger age. After aortic valve surgery, if ascending aorta is dilated, the patient must be performed re-operation. For that reason, surgery for aortic root or ascending aorta is recommended to patient with bicuspid aortic valve with dilated ascending aorta. We thought that abnormality of cell cycle of the structure protein participated in ascending aorta dilation of patient with bicuspid aortic valve. We resected the wall of the ascending aota from patient undergoing aortic valve replacement for aortic valve stenosis during operation, and performed immunohistochemical staining for akt. Anti Akt antibodys were stained much on aortic media with bicuspoed aortic valve. Akt is a protein that is involved in mTOR / PI3K, and modulate the cell differenciation and proliferation. Further, the same samples were analyzed using a microarray method. On bicuspid aortic valve patients, the expression of TSC2 is reduced, and GβL is increased. TSC2 inhibit this pathway, and MLST8 activate this pathway. In the ascending aorta of BAV patients, PI3K / mTOR system is considered to be activated. When this pathway is activated, cell proliferation and cytodifferentiation are promoted abnormally,
2017-06-30 | GSE83675 | GEO
Project description:Calcific aortic valve disease is the most common form of valvular heart disease in the Western World. Milder degrees of aortic valve calcification is called aortic sclerosis and severe calcification with impaired leaflet motion is called aortic stenosis. We used microarrays to detail the global programme of gene expression underlying cdevelopment of calcified aortic valve disease in humans.
2015-10-01 | GSE51472 | GEO
Project description:The aim of the present study was to gain insights on the pathological process of Calcific Aortic Valve Disease in CHIP carriers. To uncover molecular pathways that could link CHIP to CAVD, we exanimated the aortic valve transcriptome from CHIP, non-CHIP patients, or non-calcific controls with RNAseq.
2022-08-02 | E-MTAB-11354 | biostudies-arrayexpress
Project description:Aortic valve calcification is the most common form of valvular heart disease, but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1 mutations are associated with aortic valve malformations and adult-onset calcification in families with inherited disease. The Notch signaling pathway is critical for multiple cell differentiation processes, but its role in the development of CAVD is not well understood. The aim of this study was to investigate the molecular changes that occur with inhibition of Notch signaling in the aortic valve. Notch signaling pathway members are expressed in adult aortic valve cusps, and examination of diseased human aortic valves revealed decreased expression of NOTCH1 in areas of calcium deposition. To identify downstream mediators of Notch1, we examined gene expression changes that occur with chemical inhibition of Notch signaling in rat aortic valve interstitial cells (AVICs). We found significant downregulation of Sox9 along with several cartilage-specific genes that were direct targets of the transcription factor, Sox9. Loss of expression Sox9 has been published to be associated with aortic valve calcification. Utilizing an in vitro porcine aortic valve calcification model system, inhibition of Notch activity resulted in accelerated calcification while stimulation of Notch signaling attenuated the calcific process. Finally, the addition of Sox9 was able to prevent the calcification of porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch signaling contributes to aortic valve calcification via a Sox9-dependent mechanism. 3 samples of aortic valve interstitial cells treated with DAPT were compared with 3 samples of aortic valve interstitial cells treated with DMSO
2011-08-25 | E-GEOD-31668 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease in developed countries with significant morbidity and mortality. Given the poor understanding of the pathophysiological processes leading to CAVS, we utilized a joint non-targeted metabolomics and targeted lipidomics approach to better characterize the metabolic perturbations involved in its development and progression.</p><p><strong>METHODS:</strong> We collected human aortic valve tissue from 106 patients undergoing aortic valve replacement surgery. Our cohort represented aortic valvular hemodynamics from mild to severe aortic stenosis with varying degrees of valvular calcification.</p><p><strong>RESULTS:</strong> Seventy-two significantly differential (p<0.01) metabolites across different stages of CAVS severity were filtered and identified from the tissue metabolome. Each stage of valvular stenosis was characterized by a distinct metabolic signature. The top three perturbed metabolic pathways in the setting of CAVS involved glycerophospholipid metabolism, linoleic acid metabolism and primary bile acid biosynthesis. The lysophosphatidic acid species (LysoPA) exhibited significant (p<0.05) association with CAVS severity and were also found to select patients with accelerated rate of CAVS progression. Two LysoPA species namely, 18:2 LysoPA and 20:4 LysoPA, exhibited potential to serve as biomarkers of CAVS severity.</p><p><strong>CONCLUSIONS:</strong> The present study reports the largest and most comprehensive metabolomics analysis of human aortic valve stenosis that highlights the dysregulated LysoPA pathway involved in the pathogenesis of CAVS.</p>
2020-02-03 | MTBLS1267 | MetaboLights
Project description:Calcification of the aortic valve leads to increased leaflet stiffness resulting in development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification are poorly understood. Here, we investigated gene expressions in relation to valvular calcification and promotion of CAVD progression.
2016-01-28 | GSE77287 | GEO