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Abstract
Cardiovascular diseases (CVDs) remain the leading cause of death in the developed
countries. Taking into account the mounting evidence about the role of cytochrome
P450 (CYP) enzymes in cardiovascular physiology, CYP polymorphisms can be considered
one of the major determinants of individual susceptibility to CVDs. One of the important
physiological roles of CYP enzymes is the metabolism of arachidonic acid. CYP epoxygenases
such as CYP1A2, CYP2C, and CYP2J2 metabolize arachidonic acid to epoxyeicosatrienoic
acids (EETs) which generally possess vasodilating, anti-inflammatory, anti-apoptotic,
anti-thrombotic, natriuretic, and cardioprotective effects. Therefore, genetic polymorphisms
causing lower activity of these enzymes are generally associated with an increased
risk of several CVDs such as hypertension and coronary artery disease. EETs are further
metabolized by soluble epoxide hydrolase (sEH) to the less biologically active dihydroxyeicosatrienoic
acids (DHETs). Therefore, sEH polymorphism has also been shown to affect arachidonic
acid metabolism and to be associated with CVDs. On the other hand, CYP omega-hydroxylases
such as CYP4A11 and CYP4F2 metabolize arachidonic acid to 20-hydroxyeicosatetraenoic
acid (20-HETE) which has both vasoconstricting and natriuretic effects. Genetic polymorphisms
causing lower activity of these enzymes are generally associated with higher risk
of hypertension. Nevertheless, some studies have denied the association between polymorphisms
in the arachidonic acid pathway and CVDs. Therefore, more research is needed to confirm
this association and to better understand the pathophysiologic mechanisms behind it.
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