Print Email Facebook Twitter Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin Title Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin Author Salic, K. Morrison, M.C. Verschuren, L. Wielinga, P.Y. Wu, L. Kleemann, R. Gjorstrup, P. Kooistra, T. Publication year 2016 Abstract Background and aims Besides LDL-cholesterol, local vascular inflammation plays a key role in atherogenesis. Efficient therapies to treat the inflammatory component of the disease have not been established. The discovery of specialized inflammation-resolving mediators, such as resolvins may provide new opportunities for treatment. This study examines whether the ω-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1), can reduce atherosclerosis, when administered alone or in combination with a cholesterol-lowering statin. Methods ApoE*3Leiden mice were fed a hypercholesterolemic diet for 9 weeks and subsequently treated with RvE1-low (1 mg/kg/day), RvE1-high (5 mg/kg/day), atorvastatin (1.5 mg/kg/day) or the combination of atorvastatin and RvE1-low for the following 16 weeks. Results RvE1-low and RvE1-high reduced atherosclerotic lesion size to the same extent (−35%; p < 0.05), attenuated the formation of severe lesions, also seen as a proportional increase in the presence of mild lesions, but did not alter plasma cholesterol levels. Cholesterol-lowering atorvastatin reduced atherosclerosis (−27%, p < 0.05), and the combination of RvE1 and atorvastatin further attenuated lesion size (−51%, p < 0.01) and increased the content of mild lesions. RvE1 did not affect plasma SAA, E-selectin, VCAM-1 or MCP-1 but did reduce plasma EPHX4 and down-regulated the local expression of pro-atherogenic genes in the aortae, (e.g. Cd74, Cd44, Ccl2, Ccr5 and Adam17) and significantly inactivated IFN-γ (p < 0.001) and TNF-α (p < 0.001) signalling pathways. Conclusions RvE1 attenuates atherogenesis both alone and on top of a statin. The local effects of RvE1 are demonstrated by the modulated aortic expression of genes involved in inflammatory and immune responses, without altering plasma cholesterol or circulating SAA. © 2016 The Authors Subject LifeMHR - Metabolic Health ResearchELSS - Earth, Life and Social SciencesBiomedical InnovationBiologyHealthy LivingAtherosclerosisInflammationResolutionResolvin E1Statin To reference this document use: http://resolver.tudelft.nl/uuid:0665d3d7-ab21-44af-8e52-6e1a432d7cd0 DOI https://doi.org/10.1016/j.atherosclerosis.2016.05.001 TNO identifier 546207 ISSN 0021-9150 Source Atherosclerosis, 250, 158-165 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.