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Multiomics coupled with vibrational spectroscopy identify early mechanisms of experimental aortic valve stenosis [RNA]

ABSTRACT: Multiomics coupled with vibrational spectroscopy identify early mechanisms of experimental aortic valve stenosis [RNA]

PROVIDER: PRJNA1113690 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29090069.fastq.gz	Fastqsanger.gz
	SRR29090070.fastq.gz	Fastqsanger.gz
	SRR29090071.fastq.gz	Fastqsanger.gz
	SRR29090072.fastq.gz	Fastqsanger.gz
	SRR29090073.fastq.gz	Fastqsanger.gz

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Multiomics coupled with vibrational spectroscopy identify early mechanisms of experimental aortic valve stenosis [RNA]

Project description:Calcific aortic valve stenosis (CAVS), characterized by calcium deposition in the aortic valve in a multiannual process, is associated with high mortality and morbidity. To understand phenomena at its early stages, reliable animal models are needed. Here, we used a critically revised high-fat vitamin D2 diet rabbit model to unveil the earliest in vivo-derived mechanisms linked to CAVS progression. We modeled the inflammation-calcification temporal pattern seen in human disease and investigated molecular changes before inflammation. Coupling comprehensive multiomics and vibrational spectroscopy revealed that among the many procedures involved, mechanotransduction, peroxisome activation, DNA damage-response, autophagy, phospholipid signaling, native ECM proteins upregulation, protein cross-linking and self-folding, are the most relevant driving mechanisms. Activation of Complement 3 receptor, Immunoglobulin J and TLR6 were the earliest signs of inflammation. Among several identified key genes were AXIN2, FOS, and JUNB. Among 10 identified miRNAs, miR-21-5p and miR-204-5p dominated fundamental cellular processes, phenotypic transition, inflammatory modulation, and were validated in human samples. The enzymatic biomineralization process mediated by TNAP was complemented by V-type proton ATPase overexpression, and the substitution of Mg-pyrophosphate with Ca-pyrophosphate. These data extend our understanding on CAVS progression, facilitate the refinement of pathophysiological hypotheses and provide a basis for novel pharmaceutical therapy investigations.

2025-05-19 | GSE267949 | GEO

Multiomics coupled with vibrational spectroscopy identify early mechanisms of experimental aortic valve stenosis [miRNA]

2025-05-19 | GSE267951 | GEO

Multiomics coupled with vibrational spectroscopy identify early mechanisms of experimental aortic valve stenosis [miRNA]

Project description:Multiomics coupled with vibrational spectroscopy identify early mechanisms of experimental aortic valve stenosis [miRNA]

| PRJNA1113691 | ENA

Mechanisms of Fibrotic Aortic Valve Stenosis

Project description:To examine molecular mechanisms of aortic valve stenosis in mice with hypertension and hypercholesterolemia, RNA-Seq was used during the developmental phase of stenosis to identify new gene targets.

2016-03-07 | GSE71534 | GEO

GWAS on Calcific Aortic Valve Stenosis

Project description:GWAS on Calcific Aortic Valve Stenosis

| PRJNA420788 | ENA

Aortic Valve Tissue: Stenosis vs. Sclerosis

Project description:Aortic Valve Tissue: Stenosis vs. Sclerosis

| PRJNA576259 | ENA

GWAS on Calcific Aortic Valve Stenosis

Project description:GWAS on Calcific Aortic Valve Stenosis

| PRJNA420787 | ENA

Metabolomics Characterization of Human Calcific Aortic Valve Stenosis

Project description:BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

2020-02-03 | MTBLS1267 | MetaboLights

MicroRNA profiling in aortic stenosis

Project description:We compared 15 severely diseased aortic valve sample to 16 control aortic valve samples using microRNA microarrays (Affymetrix GeneChip miRNA 2.0). The diseased samples were taken from areas of severe disease of aortic valves removed at aortic valve replacement for severe aortic stenosis. Control samples were obtained from macroscopically normal post-mortem aortic valves. In addition, we compared areas of mild or moderate disease on valves from participants with severe aortic stenosis to the same participant's severely diseased sample in seven participants.

2017-04-27 | E-MTAB-2766 | biostudies-arrayexpress

mRNA profiling in aortic stenosis

Project description:We compared mRNA profiles of 10 participants with severe aortic stenosis undergoing aortic valve replacement to 10 samples donated post-mortem.

2017-04-27 | E-MTAB-3105 | biostudies-arrayexpress

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