Docosapentaenoic acid (22:5,n-3): Metabolism end effect on prostacyclin production in endothelial cells

Eicosapentaenoic acid (EPA, 20:5,n-3) and docosahexaenoic acid (DHA, 22:6,n-3), the two main fatty acids of fish oil, have been shown to inhibit prostacyclin production and to be actively interconverted, leading to the accumulation of docosapentaenoic acid (DPA, 22:5,n-3) in endothelial cell phospholipids. We have investigated the effect of supplementing endothelial cells with DPA on their capacity to produce prostacyclin. We found that endothelial cells incubated for 22 h with 25 mu M DPA bound to albumin (fatty acid/albumin ratio of 1.3) produced two-fold less prostacyclin compared to control cells when stimulated with endogenous arachidonic acid-mobilizing agents such as bradykinin and calcium ionophore A23187. Since the formation of prostacyclin from 0.1-15 mu M exogenous arachidonic acid was also reduced, it is suggested that prostacyclin inhibition observed in DPA-treated cells might not proceed from a reduction of arachidonic acid availability only. Such an inhibition was already observed after 1 h incubation of the cells with DPA, and with 2-20 times lower DPA concentrations. The inhibition might depend on EPA which was formed by retroconversion of DPA.