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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MRNA expression profile in vascular smooth muscle cells (VSMCs) after inducing calcification

ABSTRACT: Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced polyubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation enhanced VC. HDAC1 protein, but not mRNA, was reduced in cell and animal calcification models and in human calcified coronary artery. In the calcification-provoking condition, proteasomal degradation of HDAC1 preceded VC. The calcification-provoking condition induced MDM2 E3 ligase, which then resulted in HDAC1 K74 polyubiquitination. Overexpression of MDM2 enhanced VC, whereas loss of MDM2 blunted it. Decoy peptides spanning HDAC1 K74 and RG 7112, an MDM2 inhibitor, prevented VC in vivo and in vitro. These results demonstrate a previously unknown ubiquitination pathway and suggest MDM2-mediated HDAC1 polyubiquitination as a new therapeutic target in VC. Calcification was induced in rat aorta vascular smooth muscle cells with inorganic phosphate (Pi). Total RNA were extracted from the cells 3 and 6 days later. mRNA profile of the sample was compared with normal control.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Nakwon Choe

PROVIDER: E-GEOD-74755 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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mRNA expression profile in vascular smooth muscle cells (VSMCs) after inducing calcification

Project description:Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced polyubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation enhanced VC. HDAC1 protein, but not mRNA, was reduced in cell and animal calcification models and in human calcified coronary artery. In the calcification-provoking condition, proteasomal degradation of HDAC1 preceded VC. The calcification-provoking condition induced MDM2 E3 ligase, which then resulted in HDAC1 K74 polyubiquitination. Overexpression of MDM2 enhanced VC, whereas loss of MDM2 blunted it. Decoy peptides spanning HDAC1 K74 and RG 7112, an MDM2 inhibitor, prevented VC in vivo and in vitro. These results demonstrate a previously unknown ubiquitination pathway and suggest MDM2-mediated HDAC1 polyubiquitination as a new therapeutic target in VC.

2015-11-07 | GSE74755 | GEO

LncRNA expression profile and target gene prediction of calcification in human aortic smooth muscle cells induced by DPP4

Project description:Arterial media calcification caused by diabetes is an important cause of vascular calcification. Dipeptidyl peptidase-4 (DPP4) is associated with diabetic arterial media calcification. At the same time, long non-coding RNA(lncRNA) is closely related to the evolution of a variety of cardiovascular diseases, but the involvement of lncRNA in vascular calcification induced by DPP4 has not been reported in details. In this study, we established a model of human aortic smooth muscle cells (HASMCs) calcification induced by DPP4. There was a significant difference in the expression of lncRNAs and mRNAs between normal and calcified vascular smooth muscle cells detected by gene chip technology. Based on the results of microarray detection, we found that lncRNA may be involved in vascular calcification induced by DPP4 through regulating target genes.

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Project description:Fewer than 50% of patients develop vascular and valvular calcification, implying differential pathogenesis. Disease stage-specific proteomics (non-diseased/fibrotic/calcified areas) was performed on human carotid endarterectomy specimens and stenotic aortic valves.

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Human Diseased Cardiovascular Tissue – Fractionated

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Transcriptional profiling of calcium-phosphate calcified human primary coronary artery smooth muscle cells.

Project description:Transcriptomics analysis of human coronary artery smooth muscle cells cultured in calcium-phosphate medium (CaP) to induce a mineralized extracellular matrix. To study the underlying molecular mechanisms driving vascular calcification, we analyzed the transcriptome of calcium-phosphate calcified human cronary aortic smooth muscle cells on day 3.

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Transcriptional profiling of osteogenic medium calcified human primary coronary artery smooth muscle cells.

Project description:Transcriptomics analysis of human coronary artery smooth muscle cells cultured in osteogenic medium (OM) to induce a mineralized extracellular matrix. To study the underlying molecular mechanisms driving vascular calcification, we analyzed the transcriptome of osteogenic medium (OM)-calcified human coronary artery smooth muscle cells on day 7.

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Human Normal & Diseased Cardiovascular Tissue

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Carnitine O-octanoyltransferase is a novel inducer of vascular calcification via promoting fatty acid metabolism and mitochondrial dysfunction

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Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing.

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2020-03-10 | GSE146638 | GEO

Signature analyses for circulating extracellular vesicle in chronic kidney disease

Project description:Chronic kidney disease (CKD) accelerates vascular calcification (VC) via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways. We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. The miRNA transcriptome of sEVs revealed a depletion of several miRNAs in CKD. Their expression levels in sEVs from CKD patients were correlated to kidney function. This study revealed the transcriptomic landscape of miRNAs propagated in sEVs in CKD. We investigated the therapeutic potential of miRNAs in VC.

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