title: Pressure Overload-Induced Cardiac Dysfunction in Aged Male Adiponectin Knockout Mice Is Associated With Autophagy Deficiency.
abstract: Heart failure is a leading cause of death, especially in the elderly or obese and diabetic populations. Various remodeling events have been characterized, which collectively contribute to the progression of heart failure. Of particular interest, autophagy has recently emerged as an important determinant of cardiac remodeling and function. Here, we used aged, 13-month-old, male adiponectin knockout (Ad-KO) or wild-type (wt) mice subjected to aortic banding to induce pressure overload (PO). Cardiac strain analysis using speckle tracking echocardiography indicated significant dysfunction at an earlier stage in Ad-KO than wt. Analysis of autophagy by Western blotting for Light Chain 3 or microtubule-associated proteins 1B and Sequestosome 1 together with transmission electron microscopy of left ventricular tissue indicated a lack of PO-induced cardiac autophagy in Ad-KO compared with wt mice. Associated with this was mitochondrial degeneration and evidence of enhanced endoplasmic reticulum stress. Western blotting for Light Chain 3 or microtubule-associated proteins 1B, examination of flux using tandem fluoresent tagged-Light Chain 3, and analysis of lysosomal activity in H9c2 cardiac myoblasts treated with adiponectin indicated that adiponectin enhanced autophagy flux. In conclusion, adiponectin directly stimulates autophagic flux and the lack of autophagy in response to PO in aged mice lacking adiponectin may contribute to cellular events which exacerbate the development of cardiac dysfunction.
authors.affiliation: Department of Biology (J.W.S.J., S.T., V.K., K.D., G.S.), York University, Toronto M3J 1P3, Canada; and Division of Cardiovascular Surgery and Toronto General Research Institute (R.-K.L.), University Health Network, Toronto M3J 1P3, Canada.
authors.forename: James Won Suk
authors.initials: JW
authors.lastname: Jahng
authors.affiliation: Department of Biology (J.W.S.J., S.T., V.K., K.D., G.S.), York University, Toronto M3J 1P3, Canada; and Division of Cardiovascular Surgery and Toronto General Research Institute (R.-K.L.), University Health Network, Toronto M3J 1P3, Canada.
authors.forename: Subat
authors.initials: S
authors.lastname: Turdi
authors.affiliation: Department of Biology (J.W.S.J., S.T., V.K., K.D., G.S.), York University, Toronto M3J 1P3, Canada; and Division of Cardiovascular Surgery and Toronto General Research Institute (R.-K.L.), University Health Network, Toronto M3J 1P3, Canada.
authors.forename: Vera
authors.initials: V
authors.lastname: Kovacevic
authors.affiliation: Department of Biology (J.W.S.J., S.T., V.K., K.D., G.S.), York University, Toronto M3J 1P3, Canada; and Division of Cardiovascular Surgery and Toronto General Research Institute (R.-K.L.), University Health Network, Toronto M3J 1P3, Canada.
authors.forename: Keith
authors.initials: K
authors.lastname: Dadson
authors.affiliation: Department of Biology (J.W.S.J., S.T., V.K., K.D., G.S.), York University, Toronto M3J 1P3, Canada; and Division of Cardiovascular Surgery and Toronto General Research Institute (R.-K.L.), University Health Network, Toronto M3J 1P3, Canada.
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
authors.affiliation: Department of Biology (J.W.S.J., S.T., V.K., K.D., G.S.), York University, Toronto M3J 1P3, Canada; and Division of Cardiovascular Surgery and Toronto General Research Institute (R.-K.L.), University Health Network, Toronto M3J 1P3, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D001794:Blood Pressure; D004452:Echocardiography; D059865:Endoplasmic Reticulum Stress; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics*; D006352:Heart Ventricles / Q000378:metabolism / Q000648:ultrastructure; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D000071456:Sequestosome-1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D006360:Heat-Shock Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; C085284:microtubule-associated protein 1B