title: The ApoA-I mimetic peptide FAMP promotes recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway.
abstract: OBJECTIVE
  HDL has various atheroprotective functions and improves endothelial function. Apolipoprotein A-I (apoA-I) is a major protein of HDL and plays a crucial role in HDL functions. We developed a novel apoA-I mimetic peptide, FAMP (Fukuoka University ApoA-I Mimetic Peptide). It is unclear whether an apoA-I mimetic peptide can promote neovascularization in vivo. Here, we investigated the effect of FAMP on endothelial nitric oxide synthase (eNOS) activation and angiogenesis in a murine hindlimb ischemia model.
  
  
  RESULTS
  Intramuscular administration of FAMP significantly enhanced blood flow recovery and increased capillary density in the ischemic limb of mice fed a high-cholesterol diet (HCD). In a gait analysis, FAMP ameliorated functional recovery compared with that in the control group. FAMP significantly activated Akt, ERK, and eNOS phosphorylation in endothelial cells, and improved the migratory functions of human aortic endothelial cells (HAECs). LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), significantly inhibited the activation of eNOS by FAMP. FAMP had no beneficial effects on blood flow recovery in eNOS(-/-) mice.
  
  
  CONCLUSIONS
  FAMP promoted recovery from hindlimb ischemia through a nitric oxide (NO)-related pathway by activation of a PI3K/Akt pathway. FAMP may become a new therapeutic agent for the future clinical treatment of critical limb ischemia (CLI).
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan. Electronic address: simaizumi@fukuoka-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kawachi
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Yahiro
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Suematsu
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Department of Joint Laboratory for Frontier Medical Science, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Nephrology and Rheumatology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yasuno
authors.affiliation: Department of Pathology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Jimi
authors.affiliation: Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D040761:Biomimetic Materials / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D006614:Hindlimb / Q000098:blood supply* / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016632:Apolipoprotein A-I; D010446:Peptide Fragments; D009569:Nitric Oxide
keywords: Apolipoprotein A-I mimetic peptide; Endothelial nitric oxide synthase; High-density lipoprotein