title: Structural apelin analogues: mitochondrial ROS inhibition and cardiometabolic protection in myocardial ischaemia reperfusion injury.
abstract: OBJECTIVE
  Mitochondria-derived oxidative stress is believed to be crucially involved in cardiac ischaemia reperfusion (I/R) injury, although currently no therapies exist that specifically target mitochondrial reactive oxygen species (ROS) production. The present study was designed to evaluate the potential effects of the structural analogues of apelin-12, an adipocyte-derived peptide, on mitochondrial ROS generation, cardiomyocyte apoptosis, and metabolic and functional recovery to myocardial I/R injury.
  
  
  METHODS
  In cultured H9C2 cardiomyoblasts and adult cardiomyocytes, oxidative stress was induced by hypoxia reoxygenation. Isolated rat hearts were subjected to 35 min of global ischaemia and 30 min of reperfusion. Apelin-12, apelin-13 and structural apelin-12 analogues, AI and AII, were infused during 5 min prior to ischaemia.
  
  
  RESULTS
  In cardiac cells, mitochondrial ROS production was inhibited by the structural analogues of apelin, AI and AII, in comparison with the natural peptides, apelin-12 and apelin-13. Treatment of cardiomyocytes with AI and AII decreased cell apoptosis concentration-dependently. In a rat model of I/R injury, pre-ischaemic infusion of AI and AII markedly reduced ROS formation in the myocardial effluent and attenuated cell membrane damage. Prevention of oxidative damage by AI and AII was associated with the improvement of functional and metabolic recovery after I/R in the heart.
  
  
  CONCLUSIONS
  These data provide the evidence for the potential of the structural apelin analogues in selective reduction of mitochondrial ROS generation and myocardial apoptosis and form the basis for a promising therapeutic strategy in the treatment of oxidative stress-related heart disease.
authors.affiliation: Russian Cardiology Research-and-Production Complex, Moscow, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Pisarenko
authors.affiliation: Russian Cardiology Research-and-Production Complex, Moscow, Russia.
authors.forename: Valentin
authors.initials: V
authors.lastname: Shulzhenko
authors.affiliation: Russian Cardiology Research-and-Production Complex, Moscow, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Studneva
authors.affiliation: Russian Cardiology Research-and-Production Complex, Moscow, Russia.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Pelogeykina
authors.affiliation: Russian Cardiology Research-and-Production Complex, Moscow, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Timoshin
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1048, Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Rodica
authors.initials: R
authors.lastname: Anesia
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1048, Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1048, Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Angelo
authors.initials: A
authors.lastname: Parini
authors.affiliation: National Institute of Health and Medical Research (INSERM) U1048, Toulouse, France.|University of Toulouse, UPS, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Oksana
authors.initials: O
authors.lastname: Kunduzova
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; C495200:apelin-12 peptide; C495199:apelin-13 peptide