Dysregulated microRNAs in calcific aortic valve disease
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE87885 | GEO | 2019/10/10
REPOSITORIES: GEO
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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
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: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: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: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: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.
2011-08-26 | GSE31668 | GEO
Project description:Calcific Aortic Valve Disease (CAVD) is a common heart valve condition, often characterized by severe narrowing of the aortic valve. It lacks pharmaceutical treatments and typically requires aortic valve replacement surgery, imposing a significant burden on healthcare resources.This study reports the expression profile of circRNAs in the aortic valve tissues of CAVD patients and a normal control group (non-CAVD). We collected aortic valve tissue samples from three CAVD patients who underwent aortic valve replacement surgery due to severe aortic valve stenosis, as well as aortic valve samples from non-CAVD patients who either received heart transplant surgery (recipient heart) or had their aortic valve removed due to aortic dissection. Overall, our research reveals the significant role of circRNAs in the progression of CAVD. CircRNAs, a class of circular non-coding RNA molecules, are actively studied for their functions and regulatory mechanisms within cells. These findings contribute to a deeper understanding of the molecular mechanisms underlying CAVD, particularly the potential involvement of circRNAs in this disease.
2024-02-02 | GSE254393 | GEO
Project description:Aortic valve calcific disease (CAVD) is a common heart valve condition typically characterized by severe narrowing of the aortic valve. Our previous research has shown that circHIPK3 is downregulated in calcified aortic valve tissues and plays a role in regulating the progression of CAVD. To further investigate how circHIPK3 exerts its inhibitory effects on aortic valve calcification, we overexpressed circHIPK3 in aortic valve interstitial cells and conducted RNA-seq analysis, revealing that circHIPK3 regulates key factors in the Wnt signaling pathway. These findings contribute to a deeper understanding of the molecular mechanisms underlying CAVD, particularly the potential involvement of circRNAs in this disease.
2024-02-02 | GSE254394 | GEO
Project description:The role of long noncoding RNAs (lncRNAs) in calcific aortic valve disease (CAVD) remains largely elusive. This study aims to report a novel therapeutic lncRNA, SNHG3, and elucidate its role in CAVD. Based on high-throughput transcriptomic sequencing of human aortic valves, SNHG3 is among the most highly expressed lncRNAs in CAVD. Furthermore, SNHG3 upregulation is verified in human calcified aortic valves, osteoblastic human aortic valve interstitial cells (hVICs), and aortic valve tissues in CAVD mice. Moreover, knockdown of SNHG3 with antisense oligonucleotide markedly ameliorates aortic valve calcification in high cholesterol diet-treated ApoE-/- mice, as evidenced by reduced calcium deposition in the aortic valve leaflets, improved echocardiographic parameters, and decreased osteogenic differentiation markers (RUNX2, osteopontin, and osteocalcin) in aortic valves. Consistent with these in vivo findings, SNHG3 overexpression aggravates the calcification of hVICs, while knockdown of SNHG3 alleviates the process of differential calcification. Transcriptomics sequencing, gene set enrichment analyses, RNA-pull down, RNA immunoprecipitation and chromatin immunoprecipitation-qPCR show that SNHG3 physically interacts with polycomb repressive complex 2 to suppress the H3K27 tri-methylation BMP2 locus, which in turn activates BMP2 expression and signaling pathways. Taken together, SNHG3 promotes aortic valve calcification by upregulating BMP2, which might be a novel therapeutic target in human CAVD.
2022-10-01 | GSE199718 | GEO
Project description:Calcific aortic valvular disease (CAVD) is characterized by sclerosis of the aortic valve leaflets and recent clinical studies have linked several other risk factors to this disease, including male sex. In this study we examined potential sex-related differences in gene expression profiles between porcine male and female valvular interstitial cells (VICs) to explore possible differences in CAVD propensity on the cellular level. RNA samples from three male and three female healthy porcine aortic valve leaflets (denuded of endothelial cells) were isolated, processed, and hybridized to AffymetrixM-BM-. GeneChip Porcine Genome microarrays according to manufacturerM-bM-^@M-^Ys instructions. Mean expression values of each probe set in the male samples were compared with those in the female samples.
2013-01-02 | E-GEOD-33654 | biostudies-arrayexpress