An apoA-I mimetic peptibody generates HDL-like particles and increases alpha-1 HDL subfraction in mice

Journal of Lipid Research

Larissa Atangan¹  Ki Won Kim²  Renee Komorowski²  Carolyn Chu²  Minghan Wang²  Murielle Véniant²  Michelle M. Chen²  Wei Gu³  Joon Han³  Sylvia Hu³  Shu-Chen Lu⁴ 

[1] Departments of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA 91320;Departments of Metabolic Disorders, Amgen, Inc., Thousand Oaks, CA 91320;Protein Sciences, Amgen, Inc., Thousand Oaks, CA 91320;To whom correspondence should be addressed;

关键词: apolipoprotein AI;    atherosclerosis;    ATP binding cassette transporter A1;    cholesterol efflux;    4F peptide;    high density lipoprotein;   

DOI  :  

来源: DOAJ

【 摘 要 】

The aim of this study is to investigate the capability of an apoA-I mimetic with multiple amphipathic helices to form HDL-like particles in vitro and in vivo. To generate multivalent helices and to track the peptide mimetic, we have constructed a peptibody by fusing two tandem repeats of 4F peptide to the C terminus of a murine IgG Fc fragment. The resultant peptidbody, mFc-2X4F, dose-dependently promoted cholesterol efflux in vitro, and the efflux potency was superior to monomeric 4F peptide. Like apoA-I, mFc-2X4F stabilized ABCA1 in J774A.1 and THP1 cells. The peptibody formed larger HDL particles when incubated with cultured cells compared with those by apoA-I. Interestingly, when administered to mice, mFc-2X4F increased both pre-β and α-1 HDL subfractions. The lipid-bound mFc-2X4F was mostly in the α-1 migrating subfraction. Most importantly, mFc-2X4F and apoA-I were found to coexist in the same HDL particles formed in vivo. These data suggest that the apoA-I mimetic peptibody is capable of mimicking apoA-I to generate HDL particles. The peptibody and apoA-I may work cooperatively to generate larger HDL particles in vivo, either at the cholesterol efflux stage and/or via fusion of HDL particles that were generated by the peptibody and apoA-I individually.

【 授权许可】

Unknown