Inhibition of endothelium-dependent arterial relaxation by oxidized phosphatidylcholine

Formation of oxidized phosphatidylcholine (ox-PC), oxidatively fragmented phosphatidylcholine (PC) containing a short-chain and/or polar oxidative residue at the sn-2 position, in the process of LDL oxidation as well as its existence in atherosclerotic lesions has been demonstrated. To clarify the pathophysiological role of ox-PC in the vascular reactivity, we investigated the effects of various ox-PCs on the isometric tensions in rabbit thoracic aortas. Ox-PCs, which were produced upon oxidation of sn-2 polyunsaturated fatty acid (PUFA)-containing PCs, dose-dependently inhibited endothelium-dependent relaxation (EDR) evoked by acetylcholine or substance P. On the other hand, neither native PUFA-containing PCs nor an oxidative product of monounsaturated fatty acid-containing PC showed an inhibitory effect. None of ox-PCs affected endothelium-independent relaxation to nitroglycerin. The PC-headgroup fraction, but not the oxidized fatty acids fraction, was responsible for the inhibition of EDR by ox-PC. EDR was reduced by 2-(5-oxovaleroyl)-PC, one of the secondary oxidative products of PCs that contains a short chain aldehydic residue at the sn-2 position, but not by PC hydroperoxide, the primary oxidative product. Although the possibility could not be completely ruled out that lysophosphatidylcholine rather than ox-PC may be responsible for inhibitory effects on EDR, these results suggest a novel vascular activity of ox-PCs generated from sn-2 PUFA-containing PCs which may be implicated in the pathophysiology of vascular tone.