Inhibition of five lipoxygenase activating protein (FLAP) by MK-886 decreases atherosclerosis in apoE/LDLR-double knockout mice

European Journal of Clinical Investigation
Jacek JawieńR Korbut

Abstract

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. 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 microg per 100 mg of body-weight per day. At age 6 months the mice were sacrificed under anaesthesia. 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 microm(2) in the control group versus 263,042 +/- 20,736 microm(2) in the MK-886-treated group (P < 0.05). The MK-886 did not change the plasma cholesterol lipoprotein profile as compared with the control mice. Finally, we show that MK-886 may increase p...Continue Reading

References

Jul 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·P Borgeat, B Samuelsson
May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J A PiedrahitaN Maeda
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·S IshibashiM S Brown
Jan 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·Y NakashimaR Ross
Jan 28, 1998·American Journal of Respiratory and Critical Care Medicine·L WrightN F Voelkel
Mar 9, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert J AielloHenry J Showell
Nov 2, 2002·Nature Medicine·Peter Libby, Masanori Aikawa
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rainer SpanbroekAndreas J R Habenicht
Jun 28, 2003·Cardiovascular Research·Rima ElhageGöran K Hansson
Sep 23, 2003·Current Opinion in Lipidology·Margarete Mehrabian, Hooman Allayee
Jan 2, 2004·The New England Journal of Medicine·Raffaele De Caterina, Antonella Zampolli
Jan 2, 2004·The New England Journal of Medicine·James H DwyerMargarete Mehrabian

❮ Previous
Next ❯

Citations

Feb 5, 2011·Human Genetics·Jaana HartialaHooman Allayee
May 21, 2008·Current Atherosclerosis Reports·Magnus Bäck
Jul 24, 2013·Journal of Cardiovascular Translational Research·Li-Ming GanRegina Fritsche-Danielson
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Zhou YuGarret A FitzGerald
Jan 23, 2010·Cardiovascular Research·Daniel Poeckel, Colin D Funk
Aug 5, 2010·Current Opinion in Lipidology·Jacob Fog Bentzon, Erling Falk
May 31, 2012·TheScientificWorldJournal·Graziano Riccioni, Magnus Bäck
Jul 28, 2011·Physiological Genomics·April L DarrowJ Gregory Maresh
Sep 25, 2009·Journal of Nutrigenetics and Nutrigenomics·Hooman AllayeeHoward N Hodis
Jan 14, 2012·Endocrine Reviews·Jia-Ming Xu, Guo-Ping Shi
Sep 29, 2012·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Jacek JawienRyszard Korbut
Jun 4, 2008·Folia Histochemica Et Cytobiologica·Mariusz GajdaJan A Litwin
Mar 2, 2012·The American Journal of Clinical Nutrition·Jaana HartialaHooman Allayee
May 5, 2012·The Journal of Nutrition, Health & Aging·R B KostogrysS Chłopicki
Sep 16, 2009·Free Radical Biology & Medicine·Jane A Leopold, Joseph Loscalzo
Aug 25, 2015·Redox Biology·Ryuichi Mashima, Torayuki Okuyama
Mar 22, 2012·Medicinal Research Reviews·Valérie CapraG Enrico Rovati
Jul 19, 2012·Molecular Systems Biology·I-Ming WangChristopher Roberts
Sep 5, 2007·Cell Metabolism·Yaoyu ChenXiaosong Wang
Feb 24, 2009·Current Opinion in Pharmacology·Prakash SahaAlberto Smith
Jun 19, 2014·Nucleosides, Nucleotides & Nucleic Acids·Barbara Kutryb-ZajacRyszard T Smolenski
Jan 12, 2008·Trends in Pharmacological Sciences·Jilly F EvansJohn H Hutchinson
Nov 22, 2011·Toxicology Letters·Chao-Wei HuDe-Li Dong
Jun 14, 2017·International Journal of Molecular Sciences·Megan YuYu-Min Kuo
Nov 16, 2007·Medicinal Research Reviews·R L TiwariM K Barthwal
Sep 16, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Anna CsiszarZoltan Ungvari
Apr 17, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Sándor BátkaiPál Pacher
Aug 1, 2013·Physiological Reviews·Paul N Hopkins
Oct 27, 2018·International Journal of Molecular Sciences·Thomas SonnweberIvan Tancevski

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.