The ATP-binding cassette transporter ABCG2 (BCRP), a marker for side population stem cells, is expressed in human heart.
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.
Meissner
Konrad
K
Institut für Pharmakologie, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Loeffler-Str. 23d, D-17487 Greifswald, Germany.
Heydrich
Björn
B
Jedlitschky
Gabriele
G
Meyer Zu Schwabedissen
Henriette
H
Mosyagin
Igor
I
Dazert
Peter
P
Eckel
Lothar
L
Vogelgesang
Silke
S
Warzok
Rolf W
RW
Böhm
Michael
M
Lehmann
Christian
C
Wendt
Michael
M
Cascorbi
Ingolf
I
Kroemer
Heyo K
HK
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001160:Arterioles / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology; D002317:Cardiovascular Agents / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002317:Cardiovascular Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger