title: Fas ligand mRNA levels of circulating leukocytes reflect endothelial dysfunction in hyperlipidemic but not in non-hyperlipidemic patients.
abstract: To find a novel marker for identifying patients at high-risk for endothelial dysfunction among patients with atherosclerosis, we examined the correlation between mRNA levels of Fas ligand (FasL), an apoptosis-inducing factor, in circulating leukocytes and clinical parameters in these patients. FasL mRNA levels of circulating leukocytes were measured with the TaqMan-PCR method. A negative correlation was observed between brachial artery flow-mediated dilatation (%FMD) and FasL mRNA levels of leukocytes in hyperlipidemic but not in non-hyperlipidemic patients. %FMD was more impaired in patients with a high level of FasL mRNA than in those with a low level of FasL mRNA. Interestingly, the improvement of %FMD by treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (simvastatin) was greater in the group showing a decrease in FasL mRNA than in the group with no such decrease. Additionally, simvastatin suppressed the FasL mRNA expression in leukocytes and decreased plasma oxidized low-density lipoprotein (OxLDL) levels. Furthermore, the supernatant of cultured leukocytes from hyperlipidemic patients induced cell death in Jurkat T cells, which was neutralized by an antibody against FasL. These findings suggest that high FasL mRNA expression in circulating leukocytes may be a marker of high-risk for endothelial dysfunction in hyperlipidemic but not in non-hyperlipidemic patients. This information may provide a novel basis for targeting of statin therapy in patients with vulnerable plaques.
authors.affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kotani
authors.forename: Keisuke
authors.initials: K
authors.lastname: Fukuo
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuda
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katuya
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takemura
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Yokoi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Suzuki
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000276:immunology; D050197:Atherosclerosis / Q000175:diagnosis / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D019821:Simvastatin / Q000008:administration & dosage*; D048069:Tumor Necrosis Factors / Q000235:genetics*; D015854:Up-Regulation / Q000276:immunology; D014657:Vasculitis / Q000175:diagnosis / Q000276:immunology
chemical_list: D015415:Biomarkers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; C099252:oxidized low density lipoprotein; D019821:Simvastatin