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  • Title: Fas ligand mRNA levels of circulating leukocytes reflect endothelial dysfunction in hyperlipidemic but not in non-hyperlipidemic patients.
    Author: Kotani N, Fukuo K, Yasuda O, Sugimoto K, Katuya T, Takemura Y, Kawamoto H, Yokoi T, Suzuki A, Ogihara T.
    Journal: Hypertens Res; 2006 Apr; 29(4):217-25. PubMed ID: 16778328.
    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.
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