ATP-binding cassette transporters in human heart failure.
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ATP-binding cassette transporters in human heart failure. / Solbach, Thomas F; Paulus, Barbara; Weyand, Michael; Eschenhagen, Thomas; Zolk, Oliver; Fromm, Martin F.
In: N-S ARCH PHARMACOL, Vol. 377, No. 3, 3, 2008, p. 231-243.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - ATP-binding cassette transporters in human heart failure.
AU - Solbach, Thomas F
AU - Paulus, Barbara
AU - Weyand, Michael
AU - Eschenhagen, Thomas
AU - Zolk, Oliver
AU - Fromm, Martin F
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 377
SP - 231
EP - 243
JO - N-S ARCH PHARMACOL
JF - N-S ARCH PHARMACOL
SN - 0028-1298
IS - 3
M1 - 3
ER -
