Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytochrome P450 (CYP) represents a large family of enzymes that catalyze the oxidation of endogenous and exogenous compounds. The functions of CYP enzymes in the metabolism of xenobiotics have well been established in the liver. However, some CYP enzymes are highly expressed in the heart and catalyze arachidonic acid oxidation to a variety of eicosanoids, which attenuates ischemia-reperfusion injury of the heart. CYP-mediated cardioprotection is associated with activation of multiple pathways such as sarcolemmal and mitochondrial potassium channels, p42/p44 MAPK and PI3K-AKT signaling in cells. CYP enzymes also represent a significant source of reactive oxygen species (ROS) that may target cellular homeostatic mechanisms and mitochondria. CYP isoforms expressed in the heart are critical for generation of epoxyeicosatrienoic acids (EETs) and ROS. It has been demonstrated that CYP2J2 generates cardioprotective EETs, whereas another isozyme in the heart, CYP2C, generates EETs as well as detrimental ROS. Genetic polymorphisms of CYP2C or CYP2J2 have a pathologic impact on coronary artery diseases. Cardiac CYP enzymes can be involved in drug metabolism within the heart and influence pharmacologic efficacy. Metabolism mediated by CYP enzymes influences the survival of cardiomyocytes during ischemia, which is critical for treatment of human ischemic heart disease. In this review, we summarize current knowledge of this enzyme family and discuss the roles of CYP in ischemia-reperfusion injury of the heart.
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PMID:The roles of cytochrome p450 in ischemic heart disease. 2147 72

Cytochrome P450 epoxygenase metabolites of arachidonic acid, EETs, have multiple cardiovascular effects, including reduction of blood pressure, protection against myocardial ischemia-reperfusion injury, and attenuation of endothelial apoptosis. This study investigated the hypothesis that transgenic mice with endothelial overexpression of CYP2J2 (Tie2-CYP2J2-Tr) would be protected against global cerebral ischemia induced by bilateral common carotid artery occlusion (BCCAO) and action mechanisms of EETs on cerebral ischemia in cultures of astrocytes exposed to oxygen-glucose deprivation (OGD). Tie2-CYP2J2-Tr mice had significantly increased CYP2J2 expression, increased 14,15-EET production, increases regional cerebral blood flow (rCBF) and microvascular density, decreased ROS production, decreased brain infarct size and apoptosis after ischemia compared to wild type mice, these were associated with increased activation of the PI3K/AKT and apoptosis-related protein in ischemic brain. Addition of exogenous EETs or CYP2J2 transfection attenuated OGD-induced apoptosis in astrocytes via activation of PI3K/AKT and anti-apoptosis pathways. However, these effects were reduced by pretreatments with inhibitor of the PI3K (LY294002) and 14,15-EET (14,15-EEZE), respectively. These results indicate that CYP2J2 overexpression exerts marked neuroprotective effects against ischemic injury by a mechanism linked to increased level of circulating EETs and increases CBF and reduction of apoptosis.
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PMID:Cytochrome P450 2J2 is protective against global cerebral ischemia in transgenic mice. 2304 Dec 91