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Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

  
@article{APS9498,
	author = {Li-li WANG and Dori MILLER and Desiree WANDERS and Gayani NANAYAKKARA and Rajesh AMIN and Robert JUDD and Edward E MORRISON and Ju-ming ZHONG},
	title = {Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats},
	journal = {Acta Pharmacologica Sinica},
	volume = {37},
	number = {2},
	year = {2017},
	keywords = {},
	abstract = {Aim: 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 Ca2+ 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 Ca2+ 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. 
Conclusion: 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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/9498}
}