Sex differences in translocator protein 18 kDa (TSPO) in the heart: Implications for imaging myocardial inflammation

De Lisa Fairweather; Michael J. Coronado; Amanda E. Garton; Jennifer L. Dziedzic; Adriana Bucek; Leslie T. Cooper; Jessica E. Brandt; Fatima S. Alikhan; Haofan Wang; Christopher J. Endres; Judy Choi; Martin G. Pomper; Tomás R. Guilarte

doi:10.1007/s12265-013-9538-0

Sex differences in translocator protein 18 kDa (TSPO) in the heart: Implications for imaging myocardial inflammation

De Lisa Fairweather, Michael J. Coronado, Amanda E. Garton, Jennifer L. Dziedzic, Adriana Bucek, Leslie T. Cooper, Jessica E. Brandt, Fatima S. Alikhan, Haofan Wang, Christopher J. Endres, Judy Choi, Martin G. Pomper, Tomás R. Guilarte

School of Medicine

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Pages (from-to)	192-202
Number of pages	11
Journal	Journal of cardiovascular translational research
Volume	7
Issue number	2
DOIs	https://doi.org/10.1007/s12265-013-9538-0
State	Published - Mar 2014

Keywords

CD11b
Imaging
Myocarditis
Sex differences
Single-photon emission computed tomography
TSPO

ASJC Scopus subject areas

Molecular Medicine
Genetics
Pharmaceutical Science
Cardiology and Cardiovascular Medicine
Genetics(clinical)

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Fairweather, D. L., Coronado, M. J., Garton, A. E., Dziedzic, J. L., Bucek, A., Cooper, L. T., Brandt, J. E., Alikhan, F. S., Wang, H., Endres, C. J., Choi, J., Pomper, M. G., & Guilarte, T. R. (2014). Sex differences in translocator protein 18 kDa (TSPO) in the heart: Implications for imaging myocardial inflammation. Journal of cardiovascular translational research, 7(2), 192-202. https://doi.org/10.1007/s12265-013-9538-0

Fairweather, DL, Coronado, MJ, Garton, AE, Dziedzic, JL, Bucek, A, Cooper, LT, Brandt, JE, Alikhan, FS, Wang, H, Endres, CJ, Choi, J, Pomper, MG & Guilarte, TR 2014, 'Sex differences in translocator protein 18 kDa (TSPO) in the heart: Implications for imaging myocardial inflammation', Journal of cardiovascular translational research, vol. 7, no. 2, pp. 192-202. https://doi.org/10.1007/s12265-013-9538-0

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title = "Sex differences in translocator protein 18 kDa (TSPO) in the heart: Implications for imaging myocardial inflammation",

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.",

keywords = "CD11b, Imaging, Myocarditis, Sex differences, Single-photon emission computed tomography, TSPO",

author = "Fairweather, {De Lisa} and Coronado, {Michael J.} and Garton, {Amanda E.} and Dziedzic, {Jennifer L.} and Adriana Bucek and Cooper, {Leslie T.} and Brandt, {Jessica E.} and Alikhan, {Fatima S.} and Haofan Wang and Endres, {Christopher J.} and Judy Choi and Pomper, {Martin G.} and Guilarte, {Tom{\'a}s R.}",

note = "Funding Information: 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].",

year = "2014",

month = mar,

doi = "10.1007/s12265-013-9538-0",

language = "English (US)",

volume = "7",

pages = "192--202",

journal = "Journal of cardiovascular translational research",

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T1 - Sex differences in translocator protein 18 kDa (TSPO) in the heart

T2 - Implications for imaging myocardial inflammation

AU - Fairweather, De Lisa

AU - Coronado, Michael J.

AU - Garton, Amanda E.

AU - Dziedzic, Jennifer L.

AU - Bucek, Adriana

AU - Cooper, Leslie T.

AU - Brandt, Jessica E.

AU - Alikhan, Fatima S.

AU - Wang, Haofan

AU - Endres, Christopher J.

AU - Choi, Judy

AU - Pomper, Martin G.

AU - Guilarte, Tomás R.

N1 - Funding Information: 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].

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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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KW - Imaging

KW - Myocarditis

KW - Sex differences

KW - Single-photon emission computed tomography

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JF - Journal of cardiovascular translational research

IS - 2

ER -

Sex differences in translocator protein 18 kDa (TSPO) in the heart: Implications for imaging myocardial inflammation

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Keywords

ASJC Scopus subject areas

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