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Volume 53 (7): 845-850, 2005
Copyright ©The Histochemical Society, Inc.
Cardiomyocytes of Chronically Ischemic Pig Hearts Express the MDR-1 Gene-encoded P-glycoprotein
Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, Buenos Aires University, Buenos Aires, Argentina (AJL); Department of Pathology, Italian Hospital, Buenos Aires, Argentina (HJGR); Departments of Physiology (GLVJ,AJC) and Pathology (LAC,PMCM,GGY,RPL), Favaloro University, Buenos Aires, Argentina; Scientific Investigation Commission of Buenos Aires Province, La Plata, Argentina (PMCM); and Nuclear Medicine Division, Institute of Cardiology and Cardiovascular Surgery, Favaloro Foundation, Buenos Aires, Argentina (AM)
Correspondence to: Rubén P. Laguens, Favaloro University, Solís 453, 1078 Buenos Aires, Argentina. E-mail: rlaguens{at}ffavaloro.org
The multidrug-resistant (MDR)-1 gene-encoded P-glycoprotein (Pgp-170) is not normally present in the cardiomyocyte. Given that in other tissues Pgp-170 is not found under normoxic conditions but is expressed during hypoxia, we searched for Pgp-170 in chronically ischemic porcine cardiomyocytes. Pgp-170 was detected and localized via immunohistochemistry in ischemic and nonischemic cardiomyocytes of eight adult pigs 8 weeks after placement of an Ameroid constrictor at the origin of the left circumflex artery (Cx). Regional myocardial ischemia in the Cx bed was documented with nuclear perfusion scans. Pgp-170 mass was quantified using Western blot analysis. In all pigs, Pgp-170 was consistently present in the sarcolemma and T invaginations of the cardiomyocytes of the ischemic zone. Pgp-170 expression decreased toward the border of the ischemic zone and was negative in nonischemic regions as well as in the myocardium of sham-operated animals. Western blot analysis yielded significantly higher Pgp-170 mass in ischemic than in nonischemic areas. We conclude that Pgp-170 is consistently expressed in the cardiomyocytes of chronically ischemic porcine myocardium. Its role in the ischemic heart as well as in conditions such as myocardial hibernation, stunning, and preconditioning may have potentially relevant clinical implications and merits further investigation.
(J Histochem Cytochem 53:845–850, 2005)
Key Words: MDR • P-glycoprotein • ATP-binding cassette • transporters • myocardial ischemia • hypoxia • cardiomyocyte • pig
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