title: A human apolipoprotein E mimetic peptide reduces atherosclerosis in aged apolipoprotein E null mice.
abstract: Apolipoprotein E (apoE) is well known as an antiatherogenic protein via regulating lipid metabolism and inflammation. We previously reported that a human apoE mimetic peptide, EpK, reduced atherosclerosis in apoE null (apoE(-/-)) mice through reducing inflammation without affecting plasma lipid levels. Here, we construct another human apoE mimetic peptide, named hEp, and investigate whether expression of hEp can reduce atherosclerotic lesion development in aged female apoE(-/-) mice with pre-existing lesions. We found that chemically synthesized hEp significantly decreased cholesterol accumulation induced by oxidized low density lipoprotein and the expression of inflammatory cytokines TNFα and IL-6 induced by lipopolysaccharide in macrophages. In an in vivo study, Lv-hEp-GFP lentiviruses were intravenously injected into 9 month-old apoE(-/-) mice. Mice were then fed a chow diet for 18 weeks. Results showed that in comparison to the Lv-GFP lentivirus injection (Lv-GFP) group, Lv-hEp-GFP lentivirus injection achieved hepatic hEp expression and secretion in apoE(-/-) mice. It was observed that hEp expression significantly reduced plasma VLDL and LDL cholesterol levels and decreased aortic atherosclerotic lesions. This was accompanied by an increase of LDL receptor expression and a reduction of TNFα and IL-6 mRNA levels in the liver. Moreover, expression of hEp increased plasma paraoxonase-1 activity and decreased plasma myeloperoxidase activity and serum amyloid A levels. Our study provides evidence that hEp may be developed as a promising therapeutic apoE mimetic peptide for atherosclerosis-related cardiovascular diseases through its induction of plasma VLDL/LDL cholesterol clearance as well as its anti-oxidative and anti-inflammatory activities.
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Mengting
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Liangchen
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina Columbia, SC, USA.
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
keywords: Apolipoprotein E; LDL receptor; anti-oxidation; apolipoprotein E null mice; atherosclerosis; inflammation; mimetic peptide