Cardiac hypertrophy is a major risk factor for many serious
heart diseases. Recent data demonstrated the role of
cytochrome P450 (CYP)-derived
arachidonic acid (AA) metabolites in cardiovascular pathophysiology. In the current study our aim was to determine the aberrations in CYP-mediated AA metabolism in the heart during
cardiac hypertrophy. Pressure overload
cardiac hypertrophy was induced in Sprague Dawley rats using the descending aortic constriction procedure. Five weeks post-surgery, the cardiac levels of AA metabolites were determined in hypertrophied and normal hearts. In addition, the formation rate of AA metabolites, as well as, CYP expression in cardiac microsomal fraction was also determined. AA metabolites were measured by liquid chromatography-electrospray ionization-mass spectroscopy, whereas, the expression of CYPs was determined by Western blot analysis. Non-parametric analysis was performed to examine the association between metabolites formation and CYP expressions. Our results showed that 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic
acids (EETs), and 5-, 12-, 15-, and 20-hydroxyeicosatetraenoic
acids (HETEs) levels were increased, whereas,
19-HETE formation was decreased in hypertrophied hearts. The increase in EETs was linked to
CYP2B2. On the other hand, CYP1B1 and CYP2J3 were involved in mid-chain
HETE metabolism, whereas,
CYP4A2/3 inhibition was involved in the decrease in
19-HETE formation in hypertrophied hearts. In conclusion, CYP1B1 played cardiotoxic role, whereas,
CYP2B2, CYP2J3 and
CYP4A2/3 played cardioprotective roles during pressure overload-induced
cardiac hypertrophy. These CYP can be valid targets for the development of drugs to treat and prevent
cardiac hypertrophy and
heart failure.