| http://purl.uniprot.org/citations/25644539 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25644539 | http://www.w3.org/2000/01/rdf-schema#comment | "AimsIn this study, we sought to determine the role of ecto-nucleotidases and adenosine receptors in calcific aortic valve disease (CAVD). The expression of ecto-nucleotidases, which modify the levels of extracellular nucleotides/nucleosides, may control the mineralization of valve interstitial cells (VICs). We hypothesized that expression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1), which generates AMP, and 5'-nucleotidase (CD73), an enzyme using AMP as a substrate to produce adenosine, may co-regulate the mineralization of the aortic valve.Methods and resultsWe have investigated the expression of NPP1 and 5'-nucleotidase in CAVD tissues and determined the role of these ecto-nucleotidases on the mineralization of isolated VICs. In CAVD tissues (stenotic and sclerotic), we documented that NPP1 and 5'-nucleotidase were overexpressed by VICs. In isolated VICs, we found that mineralization induced by adenosine triphosphate was decreased by silencing NPP1 and 5'-nucleotidase, suggesting a role for adenosine. Adenosine and specific A2a adenosine receptor (A2aR) agonist increased the mineralization of VICs. Silencing of A2aR in human VICs and the use of A2aR(-/-) mouse VICs confirmed that A2aR promotes the mineralization of cells. Also, A2aR-mediated mineralization was negated by the transfection of a mutant dominant-negative Gαs vector. Through several lines of evidence, we next documented that adenosine stimulated the mineralization of VICs through a cAMP/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, and found that CREB positively regulated the expression of NPP1 in a positive feedback loop by physically interacting with the promoter.ConclusionExpression of NPP1 and 5'-nucleotidase by VICs promotes the mineralization of the aortic valve through A2aR and a cAMP/PKA/CREB pathway."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.org/dc/terms/identifier | "doi:10.1093/cvr/cvv027"xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/author | "Boulanger M.C."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/author | "Mathieu P."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/author | "Mahmut A."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/author | "Bouchareb R."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/author | "Hadji F."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/name | "Cardiovasc Res"xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/pages | "109-120"xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/title | "Adenosine derived from ecto-nucleotidases in calcific aortic valve disease promotes mineralization through A2a adenosine receptor."xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://purl.uniprot.org/core/volume | "106"xsd:string |
| http://purl.uniprot.org/citations/25644539 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25644539 |
| http://purl.uniprot.org/citations/25644539 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25644539 |
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