Krishna, Smriti M., Moxon, Joseph V., Jose, Roby J., Sahebkar, Amir, Hatamipour, Mahdi, Liu, Dawie, and Golledge, Jonathan (2018) Anionic nanoliposomes reduced atherosclerosis progression in Low Density Lipoprotein Receptor (LDLR) deficient mice fed a high fat diet. Journal of Cellular Physiology, 233 (10). pp. 6951-6964.

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Abstract

Atherosclerosis is a systemic disease characterized by the deposition of cholesterol and inflammatory cells within the arterial wall. Removal of cholesterol from the vessel wall may have an impact on the size and composition of atherosclerotic lesions. Anionic phospholipids or liposome vesicles composed of a lipid bilayer such as nanoliposomes have been suggested as treatments for dyslipidemia. In this study, we investigated the effect of anionic nanoliposomes on atherosclerosis in a mouse model. Low‐density lipoprotein receptor knockout mice (Ldlr–/–) were fed with an atherosclerosis promoting high fat and cholesterol (HFC) diet for 12 weeks. Anionic nanoliposomes including hydrogenated soy phosphatidylcholine (HSPC) and distearoyl phosphatidylglycerol (DSPG) (molar ratio: 1:3) were injected intravenously into HFC‐fed Ldlr−/− mice once a week for 4 weeks. Mice receiving nanoliposomes had significantly reduced atherosclerosis within the aortic arch as assessed by Sudan IV staining area (p = 0.007), and reduced intima/media ratio (p = 0.030) and greater collagen deposition within atherosclerosis plaques within the brachiocephalic artery (p = 0.007), compared to control mice. Administration of nanoliposomes enhanced markers of reverse cholesterol transport (RCT) and increased markers of plaque stability in HFC‐fed Ldlr−/− mice. Reduced cholesterol accumulation was observed in the liver along with the up‐regulation of the major genes involved in the efflux of cholesterol such as hepatic ATP‐binding cassette transporters (ABC) including Abc‐a1, Abc‐g1, Abc‐g5, and Abc‐g8, Scavenger receptor class B, member 1 (Scarb1), and Liver X receptor alpha (Lxr)‐α. Lecithin Cholesterol Acyltransferase activity within the plasma was also increased in mice receiving nanoliposomes. Anionic nanoliposome administration reduced atherosclerosis in HFC‐fed Ldlr−/− mice by promoting RCT and upregulating the ABC‐A1/ABC‐G1 pathway.

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