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Wiley InterScience | ||||||||||||||
  European Journal of Clinical InvestigationVolume 36 Issue 3, Pages 141 - 146 Published Online: 27 Feb 2006 Journal Compilation © 2010 Stichting European Society for Clinical Investigation Journal Foundation The official journal of the European Society for Clinical Investigation
Abstract | References | Full Text: HTML, PDF (Size: 239K) | Related Articles | Citation Tracking  Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice Chair of Pharmacology (J. Jawien, L. Mateuszuk, R. Olszanecki, T. J. Guzik, S. Chlopicki, R. Korbut), Department of Histology (M. Gajda, T. Cichocki), Jagiellonian University School of Medicine, Cracow, Poland; Huddinge Hospital, Karolinska Institute, Stockholm, Sweden (M. Rudling). Copyright © 2006 Blackwell Publishing Ltd KEYWORDS ApoE/LDLR-double knockout mice • atherosclerosis • FLAP • leukotrienes • MK-886 Eur J Clin Invest 2006; 36 (3): 141–146 Abstract
Background Recent reports point to an important role of leukotrienes in atherogenesis. Leukotrienes are produced by 5-lipoxygenase co-operating with five lipoxygenase activating protein (FLAP). We hypothesized that MK-886, an inhibitor of FLAP, could attenuate the development of atherosclerosis in the atherogenic apolipoprotein E/low density lipoprotein receptor (apoE/LDLR) double knockout (DKO) mouse model. Materials and methods Female apoE/LDLR-DKO mice at the age of 8 weeks were put on Western diet. The experimental group (n = 10) received the same diet as the control group (n = 10), but mixed with MK-886 (Merck, Rahway, NJ) at a dose of 4 µg per 100 mg of body-weight per day. At age 6 months the mice were sacrificed under anaesthesia. Results Measured by the en face method, the percentage of area occupied by lesions in aortas in the control group was 25·15 ± 2·9%, whereas in the MK-886-treated group it was 11·16 ± 0·7% (P < 0·05). Lesion area measured by cross-section of aortic roots was 455 494 ± 29 564 µm Conclusions Our results show for the first time that inhibition of FLAP by MK-886 reduces development of atherosclerosis in gene-targeted apoE/LDLR-DKO mice. Received 27 October 2005; accepted 20 December 2005 | 
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