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The ATP-binding Cassette Transporter ABCG2 (BCRP), a Marker for Side Population Stem Cells, Is Expressed in Human Heart

Konrad Meissner, Björn Heydrich, Gabriele Jedlitschky, Henriette Meyer zu Schwabedissen, Igor Mosyagin, Peter Dazert, Lothar Eckel, Silke Vogelgesang, Rolf W. Warzok, Michael Böhm, Christian Lehmann, Michael Wendt, Ingolf Cascorbi and Heyo K. Kroemer

Department of Pharmacology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics (KM,BH,GJ,HMzS,IM,PD,HKK), Department of Anesthesiology (KM,CL,MW), Department of Pathology (SV,RWW), Ernst-Moritz-Arndt-University Greifswald, Germany; Department of Cardiothoracic Surgery, Klinikum Karlsburg, Germany (LE); Department of Cardiology, Saarland University, Homburg/Saar, Germany (MB); and Medizinische Klinik im Städtischen Krankenhaus (BH), Institut für Pharmakologie (IM,IC), Universitätsklinikum Schleswig-Holstein, Kiel, Germany

Correspondence to: Heyo K. Kroemer, PhD, Institut für Pharmakologie, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Loeffler-Str. 23d, D-17487 Greifswald, Germany. E-mail: kroemer{at}uni-greifswald.de

Efforts to improve severely impaired myocardial function include transplantation of autologous hematopoietic side population (SP) stem cells. The transmembrane ABC-type (ATP binding cassette) half-transporter ABCG2 (BCRP) serves as a marker protein for SP cell selection. We have recently shown that other ABC transport proteins such as ABCB1 and ABCC5 are differentially expressed in normal and diseased human heart. Here we investigated localization and individual ABCG2 expression in 15 ventricular (including 10 cardiomyopathic) and 51 auricular heart tissue samples using immunohistochemistry, confocal laser scanning fluorescence microscopy, and real-time RT-PCR. Individual genotypes were assigned using PCR–restriction fragment length polymorphism (RFLP) analysis and subsequently correlated to ABCG2 mRNA levels. ABCG2 was localized in endothelial cells of capillaries and arterioles of all samples. Ventricular samples from cardiomyopathic hearts exhibited significantly increased levels of ABCG2 mRNA (ABCG2/18S rRNA: 1.08 ± 0.30 x 10^–7; p=0.028 (dilative cardiomyopathy) and 1.16 ± 0.46 x 10^–7; p=0.009 (ischemic cardiomyopathy) compared with 0.44 ± 0.26 x 10^–7 in nonfailing hearts). The individual haplotypes were not associated with altered mRNA expression. ABCG2 is variably expressed in endothelial cells of human heart, where it may function as a protective barrier against cardiotoxic drugs such as anthracyclines or mitoxantrone. ABCG2 expression is induced in dilative and ischemic cardiomyopathies. (J Histochem Cytochem 54:215–221, 2006)

Key Words: ABC transporters • human heart • side population stem cells • BCRP • ABCG2 genotype

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