title: Secretion of adiponectin from mouse aorta and its role in cold storage-induced vascular dysfunction.
abstract: Availability of adiponectin plays a crucial role in cardiovascular function. The present study was conducted to evaluate the presence, alterations and impact of the various adiponectin isoforms in vascular tissue under clinically relevant in vitro conditions (cold storage). Presence of various adiponectin isoforms in vascular smooth muscle cells and their regulation during cold storage was evaluated by PCR, western blot, ELISA and immunohistochemistry. The impact of the various isoforms for vessel preservation was assessed using isometric force measurement as an in vitro assay for vascular function. Adiponectin is expressed in smooth muscle cells from murine aortae and human saphenous veins. Following 2 days of cold storage adiponectin mRNA expression in mouse aorta is reduced, which appears to be regulated indirectly by miR-292-3p. Despite the reduced mRNA expression, adiponectin accumulated in cold storage supernatant over 2 days indicating a net release of adiponectin. Two days of cold storage resulted in an impairment of endothelium-dependent relaxation which was prevented by addition of full-length adiponectin in concentrations similar to normal plasma levels during storage. In contrast, addition of recombinant adiponectin which is unable to form high order multimers failed to improve vessel function. High concentrations (20 μg/mL) of this trimeric isoform even reduced the vasorelaxation response and facilitated uncoupling of endothelial nitric oxide synthase. Endothelial injury by cold storage may partly be prevented by addition of high-molecular-weight adiponectin. This effect may support graft patency to avoid coagulation- and atherosclerosis-associated impairment of perfusion.
authors.affiliation: Department of Physiology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Ebner
authors.forename: David M
authors.initials: DM
authors.lastname: Poitz
authors.forename: Konstantin
authors.initials: K
authors.lastname: Alexiou
authors.forename: Andreas
authors.initials: A
authors.lastname: Deussen
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000637:transplantation; D015153:Blotting, Western; D015925:Cryopreservation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019737:Transplants; D014664:Vasodilation / Q000502:physiology
chemical_list: D052242:Adiponectin; D020033:Protein Isoforms; D012333:RNA, Messenger