title: Epigenetic regulation of 5-lipoxygenase in the phenotypic plasticity of valvular interstitial cells associated with aortic valve stenosis.
abstract: Valvular interstitial cells (VICs) are of mesenchymal origin and may differentiate into immune-like cells. This phenotypic plasticity is a key feature of aortic valve stenosis, but the role of epigenetic mechanisms has not previously been explored. Here we compared normal and calcified human aortic valve tissue. Calcified tissue exhibited decreased DNA-methylation in the promoter of the gene encoding the proinflammatory enzyme 5-lipoxygenase (5-LO), accompanied by increased 5-LO mRNA levels. Treatment of cultured VICs with the DNA methyltransferase inhibitor: 5-Aza-2'-deoxycytidine increased 5-LO mRNA levels and leukotriene production. These findings provide a first piece of evidence for epigenetic modifications of VICs in valvular heart disease.
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Edit
authors.initials: E
authors.lastname: Nagy
authors.forename: Magnus
authors.initials: M
authors.lastname: Bäck
mesh_terms: D001021:Aortic Valve / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D000077209:Decitabine; D044127:Epigenesis, Genetic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D015289:Leukotrienes; D000077209:Decitabine; D001094:Arachidonate 5-Lipoxygenase; D001374:Azacitidine