Academic Journal
The phosphatase activity of soluble epoxide hydrolase regulates vascular calcification through the metabolism of pyrophosphate anions
| Τίτλος: | The phosphatase activity of soluble epoxide hydrolase regulates vascular calcification through the metabolism of pyrophosphate anions |
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| Συγγραφείς: | Messaoudi, Hind, Varennes, Olivier, Berg, Elodie, Perzo, Nicolas, Renet, Sylvanie, Chegrani, Ghiles, Duflot, Thomas, Feugray, Guillaume, Lillich, Felix, Kauffenstein, Gilles, Brunel, Valéry, Six, Isabelle, Mentaverri, Romuald, Richard, Vincent, Anegon, Ignacio, Morisseau, Christophe, Kamel, Saïd, Proschak, Ewgenij, Bellien, Jérémy |
| Συνεισφορές: | Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications cardiovasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Goethe University Frankfurt = Goethe-Universität Frankfurt am Main, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie CHU Caen, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie (CHU Caen Normandie), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), University of California Davis (UC Davis), University of California (UC) |
| Πηγή: | ISSN: 2041-4889 ; Cell Death and Disease ; https://u-picardie.hal.science/hal-05442030 ; Cell Death and Disease, 2025, Online ahead of print. ⟨10.1038/s41419-025-08390-6⟩. |
| Στοιχεία εκδότη: | CCSD Nature Publishing Group |
| Έτος έκδοσης: | 2025 |
| Θεματικοί όροι: | [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology |
| Περιγραφή: | International audience ; While the hydrolase activity of soluble epoxide hydrolase (sEH) reduces vascular calcification, it is not known whether the phosphatase activity of sEH (sEH-P) is also involved. Pharmacological and genetic inhibition of sEH-P reduced the increased calcium deposition in rat aortic rings cultured under high-phosphate conditions. This was associated with decreased mRNA expression of the osteochondrogenic markers Msx2 and Sox9 . Deendothelialization of the aortic rings abolished this anticalcifying effect, while the calcification of human aortic smooth muscle cells was unaffected by sEH-P inhibition, suggesting a predominant role of the endothelium. Endothelial NO release did not appear to contribute, but an increased level of the calcification inhibitor pyrophosphate anions (PPi) was observed in the culture supernatant of aortic rings when sEH-P was inhibited. In vitro experiments demonstrated that PPi is a substrate of sEH-P, and that inhibiting sEH-P prevented the high-phosphate induced decrease of PPi in human aortic endothelial cells. Furthermore, the aortic calcification related to chronic kidney disease induced by subtotal nephrectomy was reduced in sEH-P-deficient rats compared to wild-type rats. This was associated with an improvement in flow-induced isolated mesenteric artery dilatation and a reduction of cardiac hypertrophy and fibrosis. Vascular calcification is regulated by sEH-P through the metabolism of endothelial PPi. The prevention of vascular calcification, together with the reduction in vascular dysfunction and cardiac remodeling, suggests that inhibiting sEH-P may help to prevent the cardiovascular complications associated with chronic kidney disease. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/41455787; PUBMED: 41455787 |
| DOI: | 10.1038/s41419-025-08390-6 |
| Διαθεσιμότητα: | https://u-picardie.hal.science/hal-05442030 https://u-picardie.hal.science/hal-05442030v1/document https://u-picardie.hal.science/hal-05442030v1/file/s41419-025-08390-6_reference.pdf https://doi.org/10.1038/s41419-025-08390-6 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Αριθμός Καταχώρησης: | edsbas.91B6DFE0 |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1038/s41419-025-08390-6 |
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