title: Potent mitochondria-targeted peptides reduce myocardial infarction in rats.
abstract: OBJECTIVE
  Previously, we demonstrated that a novel opiate peptide, 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2, provided cardioprotection against myocardial stunning in vivo. We subsequently showed that this peptide targeted mitochondria and can scavenge reactive oxygen species. The objective of this study was to determine the role of opioid versus antioxidant activity in cardioprotection.
  
  
  METHODS
  We compared two mitochondria-targeted peptide analogs that lacked opioid activity: SS-31 (D-Arg-2',6'-dimethyl-tyrosine-Lys-Phe-NH2) and SS-20 (Phe-D-Arg-Phe-Lys-NH2). They differ in that only SS-31 has scavenging ability. Rats (n=8/group) were randomized to SS-31, SS-20 or placebo. The drugs (3 mg/kg) or saline was administered intraperitoneally 30 min before ligation of the left anterior descending artery for 60 min, and another dose given intraperitoneally 5 min before reperfusion for 60 min. Study endpoints included myocardial infarct size, cardiac arrhythmia and myocardial lipid peroxidation.
  
  
  RESULTS
  The area at risk was similar among the groups. The infarct area/area at risk, however, was significantly smaller in the treatment groups (53.9+/-1.1% in SS-31 group, 47.1+/-1.4% in SS-20 group, versus 59.9+/-1% in the controls, P<0.01). Lipid peroxidation was significantly reduced by both SS-31 and SS-20 treatment. Arrhythmia occurred only during the early period of coronary occlusion and was less frequent and less severe in the peptide treatment groups than in the controls (Lambeth score 5 points, 3 points, versus 13 points in the controls, P<0.05).
  
  
  CONCLUSIONS
  This study shows that pretreatment with both SS-31 and SS-20 significantly reduced myocardial lipid peroxidation and infarct size in ischemia-reperfusion injury, and suggests that the cardioprotective properties of 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2 was primarily mediated by its antioxidant properties. As SS-20 does not scavenge reactive oxygen species, it most likely reduces reactive oxygen species production during ischemia-reperfusion.
authors: Department of Medicine, St Carollo Hospital, Suncheon City, Seoul Medical Center, Seoul, Korea, and Department of Pharmacology, Weill Cornell Medical College, New York, New York 10025, USA.
authors: Janghyun
authors: J
authors: Cho
authors: Kyungheon
authors: K
authors: Won
authors: DunLi
authors: D
authors: Wu
authors: Yi
authors: Y
authors: Soong
authors: Shaoyi
authors: S
authors: Liu
authors: Hazel H
authors: HH
authors: Szeto
authors: Mun K
authors: MK
authors: Hong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; C520830:phenylalanyl-arginyl-phenylalanyllysinamide