title: Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats.
abstract: OBJECTIVE
  Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats.
  
  
  METHODS
  Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca(2+) transient.
  
  
  RESULTS
  A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca(2+) transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 μg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats.
  
  
  CONCLUSIONS
  These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure.
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama, USA.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama, USA.
authors.forename: Dori
authors.initials: D
authors.lastname: Miller
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama, USA.
authors.forename: Desiree
authors.initials: D
authors.lastname: Wanders
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Alabama, USA.
authors.forename: Gayani
authors.initials: G
authors.lastname: Nanayakkara
authors.affiliation: Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Alabama, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Amin
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Judd
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Morrison
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Alabama, USA.
authors.forename: Ju-ming
authors.initials: JM
authors.lastname: Zhong
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000097:blood* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D006333:Heart Failure / Q000097:blood* / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D055372:AMP-Activated Protein Kinases; D002118:Calcium