Epoxygenases and peroxisome proliferator-activated receptors in mammalian vascular biology

Epoxygenases, particularly of the CYP2C and CYP2J families, are important lipid-metabolizing enzymes. Epoxygenases are found throughout the cardiovascular system where their lipid products, particularly the epoxyeicosatrienoic acids (EETs), which are arachidonic acid metabolites, have the potential to regulate vascular tone, cellular proliferation, migration, inflammation and cardiac function. The receptors for EETs are, however, poorly understood. The peroxisome proliferator-activated receptors (PPARs) are a family of three (alpha, beta/delta and gamma) nuclear receptors that are activated by lipid metabolites. Activation of PPAR alpha and PPAR gamma, similar to the longer term effects of EETs, causes the inhibition of vascular cell proliferation, migration and inflammation. Interestingly, EETs and their metabolites have recently been found to active both PPAR alpha and PPAR gamma. The epoxygenase-EET-PPAR pathway may therefore represent a novel endogenous protective pathway by which short-lived lipid mediators control vascular cell activation.