Cardiac Dysfunction in HIV‐1 Transgenic Mouse: Role of Stress and BAG3. Issue 4 (24th August 2015)

• Record Type: Journal Article
• Authors: Cheung, Joseph Y.; Gordon, Jennifer; Wang, JuFang; Song, Jianliang; Zhang, Xue‐Qian; Tilley, Douglas G.; Gao, Erhe; Koch, Walter J.; Rabinowitz, Joseph; Klotman, Paul E.; Khalili, Kamel; Feldman, Arthur M.
• Is Part Of: Clinical and translational science. Volume 8:Issue 4(2015)
• Page Start: 305
• Page End: 310
• Publication Date: 2015-08-24
• Subjects: Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; 616.027
• DOI: 10.1111/cts.12331
• Languages: English
• ISSNs: 1752-8054

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>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.</p> </abstract>