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Journal of Histochemistry and Cytochemistry, Vol. 50, 1351-1356, October 2002, Copyright © 2002, The Histochemical Society, Inc.

ARTICLE

Expression and Localization of P-glycoprotein in Human Heart: Effects of Cardiomyopathy

Konrad Meissnera,b, Bernhard Sperkera, Christiane Karstena, Henriette Meyer zu Schwabedissena, Ute Seelandd, Michael Böhmd, Sandra Biena, Peter Dazerta, Christiane Kunert–Keila, Silke Vogelgesangc, Rolf Warzokc, Werner Siegmunda, Ingolf Cascorbia, Michael Wendtb, and Heyo K. Kroemera
a Institut für Pharmakologie and Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Homburg/S., Germany
b Klinik für Anästhesiologie, Homburg/S., Germany
c Institut für Pathologie, Ernst-Moritz-Arndt-Universität Greifswald, Homburg/S., Germany
d Greifswald, Germany, and Medizinische Klinik III, Universität des Saarlandes, Homburg/S., Germany

Correspondence to: Heyo K. Kroemer, Institut für Pharmakologie, Ernst-Moritz-Arndt-Universität Greifswald, Friedrich-Loeffler-Str. 23d, D-17489 Greifswald, Germany. E-mail: kroemer@uni-greifswald.de

ABC-type transport proteins, such as P-glycoprotein (P-gp), modify intracellular concentrations of many substrate compounds. They serve as functional barriers against entry of xenobiotics (e.g., in the gut or the blood–brain barrier) or contribute to drug excretion. Expression of transport proteins in the heart could be an important factor modifying cardiac concentrations of drugs known to be transported by P-gp (e.g., ß-blockers, cardiac glycosides, doxorubicin). We therefore investigated the expression and localization of P-gp in human heart. Samples from 15 human hearts (left ventricle; five non-failing, five dilated cardiomyopathy, and five ischemic cardiomyopathy) were analyzed for expression of P-gp using real-time RT-PCR, immunohistochemistry, and in situ hybridization. Immunohistochemistry revealed expression of P-gp in endothelium of both arterioles and capillaries of all heart samples. Although P-gp mRNA was detected in all samples, its expression level was significantly reduced in patients with dilated cardiomyopathy. We describe variable expression of P-gp in human heart and its localization in the endothelial wall. Thus, intracardiac concentrations of various compounds may be modified, depending on the individual P-gp level. (J Histochem Cytochem 50:1351–1356, 2002)

Key Words: P-glycoprotein, heart, drug transport, cardiomyopathy


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