title: Acute adiponectin delivery is cardioprotective in the aged female rat heart.
abstract: OBJECTIVE
  The aged, post-menopausal female heart is characterized by reduced ischemic tolerance, and few therapies currently exist to limit ischemic damage. Adiponectin (APN), a cytokine produced in adipose tissue, limits infarct size and improves functional recovery after ischemia/reperfusion injury in adult hearts. The aim of the present study was to extend these previous studies and determine the cardioprotective efficacy of APN treatment in aged female rats.
  
  
  METHODS
  Hearts were isolated from adult (age 6-7 months; n = 10), aged (age 23 months; n = 14) and aged ovariectomized (n = 10) female rats, and subjected to ischemia/reperfusion injury. On ischemia, hearts were infused with 9 μg of APN or vehicle. Adiponectin receptor 1, adiponectin receptor 2 and adenosine monophosphate-dependent kinase (AMPK) were assessed by western blotting, tumor necrosis factor-α and nicotinamide adenine dinucleotide phosphate oxidase levels by real time polymerase chain reaction. Non-reducing western blotting for APN multimers in visceral adipose was also carried out.
  
  
  RESULTS
  APN infusion successfully improved post-ischemic left ventricular developed pressure (∼10-15%) and attenuated the rise in end diastolic pressure in all groups (P < 0.05). With ischemia/reperfusion injury, phospho-AMPK increased in all groups with additive effects of APN on increasing phospho-AMPK abundance in aged ovary-intact female rats only (P < 0.001). Age-associated increases in pre-ischemic tumor necrosis factor-α mRNA were unaffected by APN, whereas nicotinamide adenine dinucleotide phosphate oxidase 2 mRNA levels were attenuated by APN in adult and aged ovariectomized female rats. An age-associated decrease in cardiac adiponectin receptor 2 was observed in conjunction with elevated high molecular weight APN in adipose.
  
  
  CONCLUSIONS
  The present data suggest that APN might be a relevant therapy for protecting the aging female heart, albeit through divergent mechanisms that are likely influenced by age-associated estrogen availability.
authors.affiliation: Intercollege Program in Physiology, The Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Nanette J
authors.initials: NJ
authors.lastname: Tomicek
authors.forename: J Craig
authors.initials: JC
authors.lastname: Hunter
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Machikas
authors.forename: Veronica
authors.initials: V
authors.lastname: Lopez
authors.forename: Donna H
authors.initials: DH
authors.lastname: Korzick
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000627:therapeutic use*; D000367:Age Factors; D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D052242:Adiponectin
keywords: adenosine monophosphate-dependent kinase; adiponectin receptor; ischemia; menopause; reperfusion; tumor necrosis factor