title: Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization.
abstract: Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration. Sterculic acid demonstrated to be 5-10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration.
authors.affiliation: Mechanism of Retinal Diseases Section, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jiahn-Dar
authors.initials: JD
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Amaral
authors.forename: Jung Wha
authors.initials: JW
authors.lastname: Lee
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Larrayoz
authors.forename: Ignacio R
authors.initials: IR
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003521:Cyclopropanes / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007653:Ketocholesterols / Q000494:pharmacology*; D007834:Lasers / Q000009:adverse effects; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D003521:Cyclopropanes; D016207:Cytokines; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D007653:Ketocholesterols; D042461:Vascular Endothelial Growth Factor A; D051742:Transcription Factor CHOP; C003345:sterculic acid; C003001:7-ketocholesterol