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Sex Differences in Translocator Protein 18 kDa (TSPO) in the Heart: Implications for Imaging Myocardial Inflammation

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Abstract

Myocarditis is more severe in men than in women and difficult to diagnose due to a lack of imaging modalities that directly detect myocardial inflammation. Translocator protein 18 kDa (TSPO) is used extensively to image brain inflammation due to its presence in CD11b+ brain microglia. In this study, we examined expression of TSPO and CD11b in mice with coxsackievirus B3 (CVB3) myocarditis and biopsy sections from myocarditis patients in order to determine if it could be used to image myocarditis. We found that male mice with CVB3 myocarditis upregulated more genes associated with TSPO activation than female mice. TSPO expression was increased in the heart of male mice and men with myocarditis compared with female subjects due to testosterone, where it was expressed predominantly in CD11b+ immune cells. We show that TSPO ligands detect myocardial inflammation using microSPECT, with increased uptake of [125I]-IodoDPA-713 in male mice with CVB3 myocarditis compared with undiseased controls.

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Funding

This work was supported by National Institutes of Health (NIH) awards from the National Heart, Lung, and Blood Institute [grant numbers HL087033, HL111938] to D.F and M.J.C., an American Heart Association Grant-in-Aid [12GRNT12050000] to D.F., and a National Institute of Environmental Health Science (NIEHS) training grant [ES07141] to M.J.C. T.R.G. is supported by an NIH award from the NIEHS [ES07062].

Ethical Standard

Authors declare that the experiments in this manuscript comply with the current laws of the USA.

Conflict of Interest

The authors declare that they have no financial relationship with the funding organizations that sponsored the research. Authors have full control of the primary data and agree to allow the journal to review the data if requested.

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Authors and Affiliations

  1. Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA

    DeLisa Fairweather, Michael J. Coronado, Amanda E. Garton, Adriana Bucek & Jessica E. Brandt

  2. Mailman School of Public Health, Columbia University, 722 W. 168th Street, New York, NY, 10032, USA

    Jennifer L. Dziedzic, Fatima S. Alikhan, Judy Choi & Tomás R. Guilarte

  3. Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Leslie T. Cooper Jr.

  4. Johns Hopkins School of Medicine, 628 Rutland Avenue, Baltimore, MD, 21205, USA

    Haofan Wang, Christopher J. Endres & Martin G. Pomper

  5. Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 N Wolfe St, Rm E7628, Baltimore, MD, 21205, USA

    DeLisa Fairweather

  6. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168th St, Rm 1105-E, New York, NY, 10032, USA

    Tomás R. Guilarte

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  1. DeLisa Fairweather
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  2. Michael J. Coronado
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Corresponding authors

Correspondence to DeLisa Fairweather or Tomás R. Guilarte.

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Editor-in-Chief Jennifer L. Hall oversaw the review of this article

DeLisa Fairweather and Michael J. Coronado are first authors.

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Fairweather, D., Coronado, M.J., Garton, A.E. et al. Sex Differences in Translocator Protein 18 kDa (TSPO) in the Heart: Implications for Imaging Myocardial Inflammation. J. of Cardiovasc. Trans. Res. 7, 192–202 (2014). https://doi.org/10.1007/s12265-013-9538-0

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