title: Humanin exerts cardioprotection against cardiac ischemia/reperfusion injury through attenuation of mitochondrial dysfunction.
abstract: OBJECTIVE
  Myocardial reperfusion via the re-canalization of occluded coronary arteries is gold standard for the treatment of acute myocardial infarction. However, reperfusion itself can cause myocardial damage due to increased reactive oxygen species (ROS) production, a process known as ischemia/reperfusion (I/R) injury. Cardiac mitochondria are the major organelle of ROS production in the heart. Cardiac mitochondrial dysfunction caused by an increased ROS production can increase cardiac arrhythmia incidence, myocardial infarct size, and cardiac dysfunction. Thus, preservation of cardiac mitochondrial function is a promising pharmacological approach to reduce cardiac I/R injury. Humanin (HN), a newly discovered 24-amino acid polypeptide, has been shown to exert antioxidative stress and antiapoptotic effects. Although the cardioprotective effects of HN against I/R injury has been reported, the effect of HN on cardiac mitochondrial function has not yet been investigated. Thus, we tested the hypothesis that HN exerts its cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction.
  
  
  METHODS
  I/R protocol was carried out using a 30-minutes occlusion of a left anterior descending coronary artery followed by a 120-minutes of reperfusion. The plasma HN level, infarct size, arrhythmia incidence, left ventricular function, and cardiac mitochondrial function were determined.
  
  
  RESULTS
  Endogenous HN level before I/R injury showed no difference between groups, but was markedly decreased after I/R injury. HN analogue pretreatment decreased arrhythmia incidence and infarct size, improved cardiac mitochondrial function, and attenuated cardiac dysfunction.
  
  
  CONCLUSIONS
  Humanin analogue pretreatment exerted cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Savitree
authors.initials: S
authors.lastname: Thummasorn
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nattayaporn
authors.initials: N
authors.lastname: Apaijai
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Sasiwan
authors.initials: S
authors.lastname: Kerdphoo
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Krekwit
authors.initials: K
authors.lastname: Shinlapawittayatorn
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.|Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; C427211:humanin
keywords: Apoptosis; Heart; Humanin; Ischemia/reperfusion injury; Mitochondrial dysfunction; Oxidative stress