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The Metabolism of Epoxyeicosatrienoic Acids by Soluble Epoxide Hydrolase Is Protective against the Development of Vascular Calcification.
Varennes, Olivier; Mentaverri, Romuald; Duflot, Thomas; Kauffenstein, Gilles; Objois, Thibaut; Lenglet, Gaëlle; Avondo, Carine; Morisseau, Christophe; Brazier, Michel; Kamel, Saïd; Six, Isabelle; Bellien, Jeremy.
Afiliação
  • Varennes O; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
  • Mentaverri R; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
  • Duflot T; Department of Biochemistry, Amiens-Picardie University Hospital, 80054 Amiens, France.
  • Kauffenstein G; Department of Pharmacology, Rouen University Hospital, CEDEX 1, 76031 Rouen, France.
  • Objois T; INSERM U1096, Normandy University, UNIROUEN, F-76000 Rouen, France.
  • Lenglet G; INSERM U1260, University of Strasbourg, F-67000 Strasbourg, France.
  • Avondo C; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
  • Morisseau C; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
  • Brazier M; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
  • Kamel S; Department of Entomology and Nematology and UCD Comprehensive Cancer Center, University of California, Davis, CA 95616, USA.
  • Six I; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
  • Bellien J; MP3CV, EA7517, CURS (Centre de Recherche Universitaire en Santé), University of Picardie Jules Verne, 80025 Amiens, France.
Int J Mol Sci ; 21(12)2020 Jun 17.
Article em En | MEDLINE | ID: mdl-32560362
ABSTRACT
This study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes endothelium-derived epoxyeicosatrienoic acids, plays a role in vascular calcification. The sEH inhibitor trans-4-(4-(3-adamantan-1-yl-ureido)-cyclohexyloxy)-benzoic acid (t-AUCB) potentiated the increase in calcium deposition of rat aortic rings cultured in high-phosphate conditions. This was associated with increased tissue-nonspecific alkaline phosphatase activity and mRNA expression level of the osteochondrogenic marker Runx2. The procalcifying effect of t-AUCB was prevented by mechanical aortic deendothelialization or inhibition of the production and action of epoxyeicosatrienoic acids using the cytochrome P450 inhibitor fluconazole and the antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE), respectively. Similarly, exogenous epoxyeicosatrienoic acids potentiated the calcification of rat aortic rings through a protein kinase A (PKA)-dependent mechanism and of human aortic vascular smooth muscle cells when sEH was inhibited by t-AUCB. Finally, a global gene expression profiling analysis revealed that the mRNA expression level of sEH was decreased in human carotid calcified plaques compared to adjacent lesion-free sites and was inversely correlated with Runx2 expression. These results show that sEH hydrolase plays a protective role against vascular calcification by reducing the bioavailability of epoxyeicosatrienoic acids.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Graxos Monoinsaturados / Suscetibilidade a Doenças / Epóxido Hidrolases / Metabolismo dos Lipídeos / Calcificação Vascular Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Graxos Monoinsaturados / Suscetibilidade a Doenças / Epóxido Hidrolases / Metabolismo dos Lipídeos / Calcificação Vascular Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article