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 [(125)I]-IodoDPA-713 in male mice with CVB3 myocarditis compared with undiseased controls.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA, dfairwea@jhsph.edu.
authors.forename: DeLisa
authors.initials: D
authors.lastname: Fairweather
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coronado
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Garton
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dziedzic
authors.forename: Adriana
authors.initials: A
authors.lastname: Bucek
authors.forename: Leslie T
authors.initials: LT
authors.lastname: Cooper
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Brandt
authors.forename: Fatima S
authors.initials: FS
authors.lastname: Alikhan
authors.forename: Haofan
authors.initials: H
authors.lastname: Wang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.forename: Judy
authors.initials: J
authors.lastname: Choi
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Tomás R
authors.initials: TR
authors.lastname: Guilarte
mesh_terms: D000081:Acetamides; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D039481:CD11b Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D064847:Multimodal Imaging; D009205:Myocarditis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009919:Orchiectomy; D011237:Predictive Value of Tests; D011743:Pyrimidines; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D012737:Sex Factors; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D000081:Acetamides; D015415:Biomarkers; C463819:Bzrp protein, mouse; D039481:CD11b Antigen; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human; D013739:Testosterone; C544082:N,N-diethyl-2-(2-(3-iodo-4-methoxyphenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide