Human vascular endothelial cells synthesize and release 24- and 26-carbon polyunsaturated fatty acids

Vascular endothelial cells from human umbilical vein readily incorporate [14C]eicosatrienoate (20:3 (n - 6) and desaturate it to synthesize [14C]arachidonate (20:4) and [14C]docosatetraenoate (22:4). Both substrate and metabolites are extensively esterified in cellular phospholipids and triacylglycerol. After these cells are incubated for 24-48 h with 4.5 microM [14C]20:3 in culture medium plus 10% fetal bovine serum, the medium contains a number of radiolabeled free fatty acids. In addition to arachidonate and docosatetraenoate, these include still longer-chain polyunsaturated fatty acids. We have identified these as 24:4, 24:5, 26:4 and 26:5 by both radio-gas chromatography and HPLC. Although the 24- and 26-carbon polyunsaturated fatty acids represent a negligible percentage of cellular 14C-labeled fatty acids, they are each present in the medium at a concentration of 10-40 nM, whereas [14C]arachidonate is 60-100 nM. In particular, products of delta 4 desaturation are a significant component of radiolabeled polyunsaturated fatty acids in medium but not in the cells. Since docosapolyenoic fatty acids have recently been shown to give rise to biologically active oxygenated derivatives, the selective release and possible subsequent metabolism of even longer polyunsaturated fatty acids warrants further investigation.