High density lipoprotein reverses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation

Matsuda, Y.; Hirata, K.; Inoue, N.; Suematsu, M.; Kawashima, S.; Akita, H.; Yokoyama, M.

Circulation Research 72(5): 1103-1109

1993


ISSN/ISBN: 0009-7330
PMID: 8477522
DOI: 10.1161/01.res.72.5.1103
Accession: 008770774

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Abstract
We have recently reported that oxidized low density lipoprotein (ox-LDL) inhibits endothelium-dependent arterial relaxation through its increased lysophosphatidylcholine (LPC). In this study we examined whether high density lipoprotein (HDL) has any effect on the inhibition of endothelium-dependent relaxation by ox-LDL in isolated strips of rabbit thoracic aorta. Both low density lipoprotein (LDL) and HDL were isolated from normal human plasma, and LDL was oxidized by exposure to copper. Preincubation of arterial strips with ox-LDL (0.1-0.5 mg protein/ml) inhibited endothelium-dependent relaxation to acetylcholine (ACh) in a concentration-dependent manner. HDL (1 mg protein/ml) by itself had no effect on the relaxation to ACh. In the presence of HDL, the inhibition by ox-LDL was markedly reduced. Although synthetic L-alpha-palmitoyl LPC (5 mu-g/ml) completely abolished a relaxation to ACh, the preincubation of arterial strips with HDL completely prevented the LPC-induced inhibition. Moreover, a relaxation to ACh was almost completely recovered when the strips were washed with buffer containing HDL even after LPC-induced inhibition had occurred. HDL markedly reduced the incorporation of (1-14C)palmitate-labeled LPC ((14C)LPC) into cultured bovine aortic endothelial cells and promoted the release of cell-incorporated (14C)LPC into the medium, resulting in a reduction of the remaining (14C)LPC in the cells. Agarose electrophoresis after incubation of a mixture of ox-LDL labeled with (14C)LPC and unlabeled HDL demonstrated a transfer of (14C)LPC from ox-LDL to HDL. These results indicate that HDL reverses the ox-LDL-induced impairment of endothelium-dependent relaxation by removing LPC from ox-LDL and preventing LPC from acting on the endothelium. Thus, HDL may have a salutary effect against the impairment of endothelium-mediated vasodilation in atherosclerotic arteries.