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ATP-binding cassette transporters in human heart failure.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2008 May; Vol. 377 (3), pp. 231-43. Date of Electronic Publication: 2008 Apr 08. - Publication Year :
- 2008
-
Abstract
- Adenosine triphosphate-binding cassette (ABC) transporters are involved in energy-dependent transport of substrates across biological membranes. We hypothesized that their expression is altered during human heart failure, suggesting a pathophysiologic basis. Messenger ribonucleic acid quantification of all known ABC transporters revealed multiple alterations in ABC transporter expression in failing human hearts (New York Heart Association classification III-IV) compared to nonfailing controls. These include a loss of ABCC7 chloride channels and an increased expression of the K(ATP) channel regulatory subunits ABCC8. Moreover, ABCG2, an efflux pump for xenobiotics/drugs, was expressed at much higher levels in failing hearts compared to nonfailing control hearts. ABCG2 was found in cardiac capillary endothelial cells and cardiomyocytes. Experiments in cells stably transfected with human ABCG2 revealed that the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone was transported by ABCG2 but also inhibited the export of the prototypical ABCG2 substrate pheophorbide A (IC(50) 25 microM). These results suggest that altered ABC transporter expression in failing hearts might contribute to impaired channel conductance or might affect the cardiac disposition of drugs.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters genetics
Adolescent
Adult
Aged
Animals
Cells, Cultured
Cystic Fibrosis Transmembrane Conductance Regulator genetics
Cystic Fibrosis Transmembrane Conductance Regulator metabolism
Dogs
Endothelial Cells metabolism
Female
Humans
Male
Middle Aged
Myocytes, Cardiac metabolism
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Potassium Channels, Inwardly Rectifying genetics
Potassium Channels, Inwardly Rectifying metabolism
RNA, Messenger metabolism
Receptors, Drug genetics
Receptors, Drug metabolism
Sulfonylurea Receptors
Transfection
ATP-Binding Cassette Transporters metabolism
Gene Expression
Heart Failure physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-1298
- Volume :
- 377
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 18392808
- Full Text :
- https://doi.org/10.1007/s00210-008-0279-6