title: Cardiac Dysfunction in HIV-1 Transgenic Mouse: Role of Stress and BAG3.
abstract: Since highly active antiretroviral therapy improved long-term survival of acquired immunodeficiency syndrome (AIDS) patients, AIDS cardiomyopathy has become an increasingly relevant clinical problem. We used human immunodeficiency virus (HIV)-1 transgenic (Tg26) mouse to explore molecular mechanisms of AIDS cardiomyopathy. Tg26 mice had significantly lower left ventricular (LV) mass and smaller end-diastolic and end-systolic LV volumes. Under basal conditions, cardiac contractility and relaxation and single myocyte contraction dynamics were not different between wild-type (WT) and Tg26 mice. Ten days after open heart surgery, contractility and relaxation remained significantly depressed in Tg26 hearts, suggesting that Tg26 mice did not tolerate surgical stress well. To simulate heart failure in which expression of Bcl2-associated athanogene 3 (BAG3) is reduced, we down-regulated BAG3 by small hairpin ribonucleic acid in WT and Tg26 hearts. BAG3 down-regulation significantly reduced contractility in Tg26 hearts. BAG3 overexpression rescued contractile abnormalities in myocytes expressing the HIV-1 protein Tat. We conclude: (i) Tg26 mice exhibit normal contractile function at baseline; (ii) Tg26 mice do not tolerate surgical stress well; (iii) BAG3 down-regulation exacerbated cardiac dysfunction in Tg26 mice; (iv) BAG3 overexpression rescued contractile abnormalities in myocytes expressing HIV-1 protein Tat; and (v) BAG3 may occupy a role in pathogenesis of AIDS cardiomyopathy.
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.|Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Joseph Y
authors: JY
authors: Cheung
authors: Comprehensive NeuroAIDS Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Jennifer
authors: J
authors: Gordon
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: JuFang
authors: J
authors: Wang
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Jianliang
authors: J
authors: Song
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Xue-Qian
authors: XQ
authors: Zhang
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Douglas G
authors: DG
authors: Tilley
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Erhe
authors: E
authors: Gao
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Walter J
authors: WJ
authors: Koch
authors: Center of Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Joseph
authors: J
authors: Rabinowitz
authors: Baylor College of Medicine, Houston, Texas, USA.
authors: Paul E
authors: PE
authors: Klotman
authors: Comprehensive NeuroAIDS Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Kamel
authors: K
authors: Khalili
authors: Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.|Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Arthur M
authors: AM
authors: Feldman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D009202:Cardiomyopathies / Q000209:etiology*; D015497:HIV-1; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D013312:Stress, Physiological
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C498806:Bag3 protein, mouse
keywords: adenovirus; excitation-contraction coupling; in vivo hemodynamics; surgical stress