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Dilated Cardiomyopathy in Transgenic Mice Expressing HIV Tat

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Abstract

Mechanisms responsible for HIV cardiomyopathy are unknown, but may include direct effects of HIV proteins on the heart. Transgenic mice (TG) expressing HIV Tat protein targeted to the myocardium, +/− Tat TG, have revealed anatomical and biochemical defects in the heart. The present studies were conducted to clarify the effect of Tat on cardiac function. In vivo hemodynamics was measured in awake mice after inserting a catheter tip in the left ventricle under general anesthesia. Under the age of 3 months, the heart rate (HR) was significantly lower in TG (591 ± 47 vs. 716 ± 45 bpm, TG versus FVB control (FVB), respectively (P < 0.05; n = 8–12). Other hemodynamic indexes, including left ventricular systolic pressure (LVSP), positive and negative dp/dt (mmHg/s), and left ventricular end diastolic pressure (LVEDP) remained indistinguishable from FVB. At 6 months, however, ventricular dysfunction was evident in TG (HR = 580 ± 47 vs. 673 ± 25 bpm, TG versus FVB, P < 0.05); LVSP (132 ± 6 vs. 147 ± 6 mmHg, TG versus FVB; P < 0.05); LVEDP (15 ± 4 vs. 8 ± 6 mmHg, TG vs. FVB, P < 0.05); +dp/dt = 8872 ± 331 vs. 10026 ± 796 mmHg/s TG versus FVB, P < 0.01) and −dp/dt (7403 ± 432 vs. 8835 ± 368 mmHg/s, TG versus FVB, P < 0.01; n = 8–12, in each group). The change in percentage of fractional shortening in response to isoproterenol was also significantly reduced in cardiac myocytes isolated from TG versus FVB (P < 0.05). Thus, targeted myocardial transgenic expression of HIV Tat in mice results in relative bradycardia, depression in systolic and diastolic functions in vivo, and blunted adrenergic responsiveness in vitro.

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Authors and Affiliations

  1. Department of Medicine, WVU Cardiology, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Medical Center Drive, Morgantown, WV, 26506-9157, USA

    Qiujuan Fang, Hong Kan, Fangping Chen, Puneet Sharma & Mitchell S. Finkel

  2. Department of Psychiatry, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, WV, USA

    Mitchell S. Finkel

  3. Department of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, West Virginia University School of Medicine, Morgantown, WV, USA

    Hong Kan & Mitchell S. Finkel

  4. Louis A. Johnson Veterans Affairs Medical Center, Clarksburg, WV, USA

    Mitchell S. Finkel

  5. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    William Lewis

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  1. Qiujuan Fang
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  2. Hong Kan
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  4. Fangping Chen
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Correspondence to Mitchell S. Finkel.

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Fang, Q., Kan, H., Lewis, W. et al. Dilated Cardiomyopathy in Transgenic Mice Expressing HIV Tat. Cardiovasc Toxicol 9, 39–45 (2009). https://doi.org/10.1007/s12012-009-9035-5

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  • DOI: https://doi.org/10.1007/s12012-009-9035-5

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