Skip Navigation LinksHome > February 2014 - Volume 63 - Issue 2 > Fenofibrate Modulates Cytochrome P450 and Arachidonic Acid M...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0000000000000036
Original Article

Fenofibrate Modulates Cytochrome P450 and Arachidonic Acid Metabolism in the Heart and Protects Against Isoproterenol-induced Cardiac Hypertrophy

Althurwi, Hassan N. BSc; Elshenawy, Osama H. BCPS; El-Kadi, Ayman O.S. PhD

Collapse Box


Abstract: It has been previously shown that the cytochrome P450 (P450) modulator, fenofibrate, protects against cardiovascular diseases. P450 and their metabolites, epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) were found to play an important role in cardiovascular diseases. Therefore, it is important to examine whether fenofibrate would modulate the cardiac P450 and its associated arachidonic acid metabolites and whether this modulation protects against isoproterenol-induced cardiac hypertrophy. For this purpose, male Sprague-Dawley rats were treated with fenofibrate (30 mg·kg−1·d−1), isoproterenol (4.2 mg·kg−1·d−1), or the combination of both. The expression of hypertrophic markers and different P450s along with their metabolites was determined. Our results showed that fenofibrate significantly induced the cardiac P450 epoxygenases, such as CYP2B1, CYP2B2, CYP2C11, and CYP2C23, whereas it decreased the cardiac ω-hydroxylase, CYP4A3. Moreover, fenofibrate significantly increased the formation of 14,15-EET, 11,12-EET, and 8,9-EET, whereas it decreased the formation of 20-HETE in the heart. Furthermore, fenofibrate significantly decreased the hypertrophic markers and the increase in heart-to-body weight ratio induced by isoproterenol. This study demonstrates that fenofibrate alters the expression of cardiac P450s and their metabolites and partially protects against isoproterenol-induced cardiac hypertrophy, which further confirms the role of P450s, EETs, and 20-HETE in the development of cardiac hypertrophy.

© 2014 by Lippincott Williams & Wilkins.

Follow Us!


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.