TY - JOUR
T1 - Modulation of cardiac and hepatic cytochrome P450 enzymes during heart failure
AU - Zordoky, Beshay N M
AU - El-Kadi, Ayman O S
PY - 2008/2
Y1 - 2008/2
N2 - Heart failure is a very serious cardiovascular disease that affects more than five million people in North America. The role of cytochrome P450 (CYP) in cardiovascular health and disease is well established. Many CYP enzymes have been identified in the heart and their levels have been reported to be altered during cardiac hypertrophy and heart failure. There is a great deal of discrepancy between various reports on CYP alterations during heart failure, likely due to differences in disease severity, species in question and other underlying conditions. In general, however, cardiac CYP1B and CYP2A, CYP2B, CYP2E, CYP2J, CYP4A and CYPI1 mRNA levels and related enzyme activities are usually increased. Moreover, there is a strong correlation between CYP-mediated endogenous metabolites and the pathogenesis of cardiac hypertrophy and heart failure. Some of these metabolites confer cardioprotective effect such as estradiol, dehydroepiandrosterone, epoxyeicosatrienoic acids, and prostaglandin I2; whereas, other metabolites may be harmful to the heart such as androgens, aldosterone, hydroxyeicosatetraenoic acids, and thromboxan A2. On the other hand, heart failure plays an important role in the down-regulation of hepatic CYP involved in drug metabotism through several mechanisms which include hepatocellular damage, hypoxia, elevated levels of pro-inflammatory cytokines, and increased production of heme oxygenase-1. Therefore, more research is needed to elucidate the mechanisms by which CYP affect the development and/or progression of heart failure and also the mechanism by which heart failure alters cardiac and hepatic CYP enzymes.
AB - Heart failure is a very serious cardiovascular disease that affects more than five million people in North America. The role of cytochrome P450 (CYP) in cardiovascular health and disease is well established. Many CYP enzymes have been identified in the heart and their levels have been reported to be altered during cardiac hypertrophy and heart failure. There is a great deal of discrepancy between various reports on CYP alterations during heart failure, likely due to differences in disease severity, species in question and other underlying conditions. In general, however, cardiac CYP1B and CYP2A, CYP2B, CYP2E, CYP2J, CYP4A and CYPI1 mRNA levels and related enzyme activities are usually increased. Moreover, there is a strong correlation between CYP-mediated endogenous metabolites and the pathogenesis of cardiac hypertrophy and heart failure. Some of these metabolites confer cardioprotective effect such as estradiol, dehydroepiandrosterone, epoxyeicosatrienoic acids, and prostaglandin I2; whereas, other metabolites may be harmful to the heart such as androgens, aldosterone, hydroxyeicosatetraenoic acids, and thromboxan A2. On the other hand, heart failure plays an important role in the down-regulation of hepatic CYP involved in drug metabotism through several mechanisms which include hepatocellular damage, hypoxia, elevated levels of pro-inflammatory cytokines, and increased production of heme oxygenase-1. Therefore, more research is needed to elucidate the mechanisms by which CYP affect the development and/or progression of heart failure and also the mechanism by which heart failure alters cardiac and hepatic CYP enzymes.
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U2 - 10.2174/138920008783571792
DO - 10.2174/138920008783571792
M3 - Review article
C2 - 18288954
AN - SCOPUS:41549153249
SN - 1389-2002
VL - 9
SP - 122
EP - 128
JO - Current Drug Metabolism
JF - Current Drug Metabolism
IS - 2
ER -