Expression profiling of human valve interstitial and endothelial cells and the effect of BMP and TGFB signaling
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65445 | GEO | 2018/01/29
REPOSITORIES: GEO
Similar Datasets
Project description:Although calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease, the molecular mechanisms underlying aortic valve calcification remain unknown. Here, we found a significant elevation in stanniocalcin-1 (STC1) expression in the valve interstitial cells (VICs) of calcific aortic valves by combined analysis of our comprehensive gene expression data and microarray datasets reported previously. Immunohistochemical staining showed that STC1 was located around the calcific area in the aortic valves of patients with CAVS. In vitro experiments using inhibitors and siRNA targeting osteoblast differentiation signaling revealed that activation of the Akt/STC1 axis was essential for runt-related transcription factor 2 (RUNX2) induction in the VICs. RNA sequencing and bioinformatics analysis of STC1-knocked down VICs in osteoblast differentiation medium resulted in silencing of the induction of osteoarthritis signaling-related genes, including RUNX2 and COL10A1. STC1 depletion in the murine CAVS model improved aortic valve dysfunction with high peak velocity and valve thickening and suppressed the appearance of osteochondrocytes. STC1-deficient mice also exhibited complete calcification abolishment, although partial valve thickening by aortic valve injury was observed. Our findings suggest that STC1 may be a critical factor in determining valve calcification and a novel target for preventing the transition to severe CAVS with calcification. We analyzed the gene expression profiles of the valve interstitial cells (VICs) isolated from noncalcific and calcific areas in calcific aortic valve stenosis (CAVS) donors using a gene microarray.
2023-12-31 | GSE226781 | 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:To explore the miR expression profile of calcified valve interstitial cells (VICs) induced by high calcium/phosphate, identify the key miRNA in the calcification process of VICs, and probe effect of miRs in regulating valve calcification.
2022-12-26 | GSE221671 | GEO
Project description:Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human aortic valve interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact on valve calcification has not been reported. Transcriptome sequencing was used to analyze potential molecular pathways affected by SolB treatment. To explore the therapeutic mechanism of SolB, human valve interstitial cells were induced to undergo osteogenic differentiation by OM, with or without SolB treatment meanwhile. Among the signaling pathways enriched, the P53 signaling pathway was identified as the upstream regulator of other enriched pathways such as Cell cycle, Oocyte meiosis, Cytokine-cytokine receptor interactions. These pathways were regulated by the P53 signaling pathway and were reported to be stimulated by DNA damage, an early stage of pathological change in CAVD. The cytokine-cytokine receptor interaction signaling pathway was reported to correlate with calcified aortic valve disease. taken together, our data revealed potential therapitic mechanism p53 signaling of Schisandrol B treatment in hVICs calcification.
2024-04-29 | GSE265809 | GEO
Project description:Calcific aortic valve disease (CAVD) is an slowly progressive calcification of heart valve which leads to aortic stenosis. The only existing treatment of CAVD is surgical replacment of calcified valve - development of anti-CAVD treatment is urgent task. For better understanding of molecular mechanisms of CAVD progression we performed proteomics analysis of osteogenic differentiation of human valve interstitial cells isolated from healthy humans or patients with CAVD.
2022-10-21 | PXD032212 | Pride
Project description:Mitral valve interstitial Tissue: Myxomatous P2 prolapse of the mitral valve vs. Control
| PRJNA431911 | ENA
Project description:Purpose:To explore the the function and underlying mechanisms of basic fibroblast growth factor (BFGF) on calcific aortic valve disease (CAVD) a. Methods: The valvular interstitial cells were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VICs, the osteogenic induced medium (OIM) and BFGF were added. RNA sequencing is used to identify changes in gene proffles. Results:This analysis completed the full transcriptome sequencing of 9 samples, with a total of 2 differentially expressed gene groups. The number of differentially expressed genes detected was 2526, 159. 6596 lncRNAs were identified, and the number of differentially expressed lncRNAs detected was 349,100. 6179 new circRNAs were predicted, and the number of differentially expressed circRNAs detected was 4,243. Conclusions:This study completed for the first time to the sequencing of the full transcriptome expression of valve interstitial cells under the action of BFGF, and has proved that BFGF can inhibit the calcification process of valve interstitial cells, our study suggests that bFGF has important value in the prevention and treatment of CAVD.
2023-05-01 | GSE225698 | GEO
Project description:Characterization of aortic valve interstitial cells (VICs) maintained in an optimized culture is es-sential for understanding the molecular mechanism underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Harvested leaflets from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. Significant elevation in VIC growth was observed in the 2% hypoxia group (hypo-VICs), compared to the normoxia group (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregula-tion of cell cycle accelerators (such as cyclins) were detected in hypo-VICs.
2022-01-10 | GSE183112 | GEO
Project description:Stanniocalcin-1 mediates aortic valve calcification via promoting osteochondrogenic differentiation from valve interstitial cells
| PRJNA941792 | ENA
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