Acute adiponectin delivery is cardioprotective in the aged female rat heart

作者：Tomicek Nanette J; Hunter J Craig; Machikas Alexandra M; Lopez Veronica; Korzick Donna H^*

来源：Geriatrics and Gerontology International, 2015, 15(5): 636-646.

DOI：10.1111/ggi.12306

• adenosine monophosphate-dependent kinase
• adiponectin receptor
• ischemia
• menopause
• reperfusion
• tumor necrosis factor

Aim: 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 mu g of APN or vehicle. Adiponectin receptor 1, adiponectin receptor 2 and adenosine monophosphate-dependent kinase (AMPK) were assessed by western blotting, tumor necrosis factor-a 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 (similar to 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-a 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.

• 出版日期2015-5