title: FAMP, a novel apoA-I mimetic peptide, suppresses aortic plaque formation through promotion of biological HDL function in ApoE-deficient mice.
abstract: BACKGROUND
  Apolipoprotein (apo) A-I is a major high-density lipoprotein (HDL) protein that causes cholesterol efflux from peripheral cells through the ATP-binding cassette transporter A1 (ABCA1), thus generating HDL and reversing the macrophage foam cell phenotype. Pre-β1 HDL is the smallest subfraction of HDL, which is believed to represent newly formed HDL, and it is the most active acceptor of free cholesterol. Furthermore it has a possible protective function against cardiovascular disease (CVD). We developed a novel apoA-I mimetic peptide without phospholipids (Fukuoka University ApoA-I Mimetic Peptide, FAMP).
  
  
  RESULTS
  FAMP type 5 (FAMP5) had a high capacity for cholesterol efflux from A172 cells and mouse and human macrophages in vitro, and the efflux was mainly dependent on ABCA1 transporter. Incubation of FAMP5 with human HDL or whole plasma generated small HDL particles, and charged apoA-I-rich particles migrated as pre-β HDL on agarose gel electrophoresis. Sixteen weeks of treatment with FAMP5 significantly suppressed aortic plaque formation (scrambled FAMP, 31.3 ± 8.9% versus high-dose FAMP5, 16.2 ± 5.0%; P<0.01) and plasma C-reactive protein and monocyte chemoattractant protein-1 in apoE-deficient mice fed a high-fat diet. In addition, it significantly enhanced HDL-mediated cholesterol efflux capacity from the mice.
  
  
  CONCLUSIONS
  A newly developed apoA-I mimetic peptide, FAMP, has an antiatherosclerotic effect through the enhancement of the biological function of HDL. FAMP may have significant atheroprotective potential and prove to be a new therapeutic tool for CVD.
authors.affiliation: Department of Cardiology, Fukuoka University, Japan. ueharay@fukuoka-u.ac.jp
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.forename: Setsuko
authors.initials: S
authors.lastname: Ando
authors.forename: Eiji
authors.initials: E
authors.lastname: Yahiro
authors.forename: Kosuke
authors.initials: K
authors.lastname: Oniki
authors.forename: Makoto
authors.initials: M
authors.lastname: Ayaori
authors.forename: Satomi
authors.initials: S
authors.lastname: Abe
authors.forename: Emi
authors.initials: E
authors.lastname: Kawachi
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Seijiro
authors.initials: S
authors.lastname: Shioi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanigawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency; D001692:Biological Transport; D008075:Lipoproteins, HDL / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000517:prevention & control*
chemical_list: D001057:Apolipoproteins E; D008075:Lipoproteins, HDL
keywords: ATP‐binding cassette transporters; HDL particle size; apolipoproteins; peptides; pre‐β HDL