ATTENUATION OF OXIDANT-MEDIATED ENDOTHELIAL-CELL INJURY WITH DOCOSAHEXAENOIC ACID - THE ROLE OF INTRACELLULAR IRON

Previous studies have demonstrated that altering the fatty acid compos ition of porcine pulmonary artery endothelial cells (PAEC) significant ly modulates their susceptibility to oxidative stimuli, e.g. H2O2. Bas ed on observations that fatty acids also function to transport iron, a n important catalyst for H2O2-mediated hydroxyl radical generation, we hypothesized that fatty acid-induced alterations in PAEC iron metabol ism contribute to modulation of PAEC oxidant susceptibility. To test t his hypothesis, PAEC were treated with culture medium supplemented wit h 0.1 mM oleic (18.1), linolenic (18:3) or docosahexaenoic (22:6) acid s or with an equivalent volume of ethanol vehicle for 3 h. After thoro ugh washing and incubation in unsupplemented culture medium for 24 h, PAEC monolayers were subjected to additional studies. Supplementation with 22:6 attenuated lactate dehydrogenase (LDH) release from PAEC 2 h following treatment with 100 mu M H2O2 for 30 min (% LDH release: ETO H-control = 7.9 +/- 1.6, 22:6-control = 5.9 +/- 0.9, ETOH-H2O2 = 26.4 +/- 4.2, 22:6-H2O2* = 16.2 +/- 2.9; *P < 0.05 vs ETOH-H2O2). In a non- cellular system, 18:1 and 18:3 were more effective than their methyl e ster derivatives or 22:6 at translocating iron from aqueous to hydroph obic environments. In contrast, only supplementation with 22:6 signifi cantly increased PAEC uptake of Fe-57 and human umbilical vein endothe lial cell (HUVEC) ferritin content, whereas none of the supplementatio n conditions altered PAEC catalytic iron measured with bleomycin. Thes e novel observations indicate that specific fatty acids are capable of altering PAEC iron uptake and ferritin content thereby contributing t o the understanding of the mechanisms by which fatty acids modulate th e oxidant susceptibility of vascular endothelial cells.