title: S-adenosyl methionine prevents endothelial dysfunction by inducing heme oxygenase-1 in vascular endothelial cells.
abstract: S-adenosyl methionine (SAM) is a key intermediate in the metabolism of sulfur amino acids and is a major methyl donor in the cell. Although the low plasma level of SAM has been associated with atherosclerosis, the effect of SAM administration on atherosclerosis is not known. Endothelial dysfunction is an early prerequisite for atherosclerosis. This study was undertaken to investigate the possible preventive effect of SAM on endothelial dysfunction and the molecular mechanism of its action. SAM treatment prevented endothelial dysfunction in high fat diet (HFD)-fed rats. In cultured human aortic endothelial cells, linoleic acid (LA) increased and SAM decreased cell apoptosis and endoplasmic reticulum stress. Both LA and SAM increased heme oxygenase-1 (HO-1) expression in an NF-E2-related factor 2-dependent manner. However, knockdown of HO-1 reversed only the SAM-induced preventive effect of cell apoptosis. The LA-induced HO-1 expression was dependent on PPARα, whereas SAM induced HO-1 in a PPAR-independent manner. These data demonstrate that SAM treatment prevents endothelial dysfunction in HFDfed animals by inducing HO-1 in vascular endothelial cells. In cultured endothelial cells, SAM-induced HO-1 was responsible for the observed prevention of cell apoptosis. We propose that SAM treatment may represent a new therapeutic strategy for atherosclerosis.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, Seoul, 138-736, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Seok Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Hyun-Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Jang
authors.forename: Jaechan
authors.initials: J
authors.lastname: Leem
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D002478:Cells, Cultured; D059305:Diet, High-Fat; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019787:Linoleic Acid / Q000494:pharmacology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012436:S-Adenosylmethionine; D019787:Linoleic Acid; D051547:Heme Oxygenase-1
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