Fas ligand mRNA levels of circulating leukocytes reflect endothelial dysfunction in hyperlipidemic but not in non-hyperlipidemic patients.
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.
Kotani
Noriko
N
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Fukuo
Keisuke
K
Yasuda
Osamu
O
Sugimoto
Ken
K
Katuya
Tomohiro
T
Takemura
Yukihiro
Y
Kawamoto
Hidenobu
H
Yokoi
Toyohiko
T
Suzuki
Atsuko
A
Ogihara
Toshio
T
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
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