Details

Autor(en) / Beteiligte

• Salic, Kanita
• Morrison, Martine C
• Verschuren, Lars
• Wielinga, Peter Y
• Wu, Lijun
• Kleemann, Robert
• Gjorstrup, Per
• Kooistra, Teake

Titel

Resolvin E1 attenuates atherosclerosis in absence of cholesterol-lowering effects and on top of atorvastatin

Ist Teil von

• Atherosclerosis, 2016-07, Vol.250, p.158-165

Ort / Verlag

Ireland: Elsevier Ireland Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.