title: A novel inducible cholesterol efflux peptide, FAMP, protects against myocardial ischemia reperfusion injury through a nitric oxide pathway.
abstract: OBJECTIVE
  We evaluated whether a novel inducible cholesterol efflux (iCE) peptide [Fukuoka University Apolipoprotein A-I Mimetic Peptide (FAMP)] protects against myocardial ischemia reperfusion injury (IRI) through a nitric oxide (NO) pathway by an improvement of high-density lipoprotein (HDL) functionality.
  
  
  RESULTS
  Male C57BL6/J mice were intraperitoneally injected with phosphate buffer as a control, low-dose (10 mg/kg) or high-dose (50 mg/kg) of FAMP before 18 h of IRI (n=6-12 in each group). After 30 min of ischemia followed by 6h of reperfusion, blood pressure, and infarct size were measured and cardiac function was evaluated by a Millar catheter. FAMP significantly improved stroke volume, cardiac output, left ventricular ejection fraction, and infarct size. FAMP significantly preserved cytochrome C in the mitochondrial fraction and inhibited its release into the cytosolic fraction in the heart, but did not significantly reduce mRNA levels of monocyte chemoattractant protein-1 or interluekin-6. In a TdT-mediated dUTP nick end labeling (TUNEL) assay, FAMP significantly suppressed the appearance of TUNEL-positive nuclear. We also performed same experiments with endothelial nitric oxide synthase-knockout (eNOS-KO) mice and FAMP-induced improvements of cardiac function were not observed in eNOS-KO mice.
  
  
  CONCLUSIONS
  FAMP activated HDL-functionality and improved cardiac function in a model of myocardial IRI. It may have anti-apoptotic effects by protecting mitochondria through a NO pathway as a pleiotropic effect.
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; Department of Molecular Cardiovascular Therapeutics, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan. Electronic address: miuras@cis.fukuoka-u.ac.jp.
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: Kohei
authors.initials: K
authors.lastname: Takata
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: Takashi
authors.initials: T
authors.lastname: Kuwano
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
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: Yoshino
authors.initials: Y
authors.lastname: Matsuo
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; Department of Molecular Cardiovascular Therapeutics, 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; Department of Molecular Cardiovascular Therapeutics, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018932:Chemokine CCL2; D009569:Nitric Oxide; D012313:RNA
keywords: Anti-apoptosis; Apolipoproteins; High-density lipoprotein; Nitric oxide