Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta.

Abstract

Exposure of isolated arteries to oxidatively modified low density lipoprotein (LDL) has been reported to suppress endothelium-dependent relaxation (EDR). To determine whether lipid degradation products in oxidized LDL contribute to impaired relaxation, we have tested the responsiveness of isolated rabbit aortas to endothelium-dependent relaxants (acetylcholine, ATP, and calcium ionophore A23187) and nitroglycerin before and after 2-hour incubations with selected lipids and LDL preparations. Concentrations (10 ,M) of lecithin, phosphatidylserine, lysophosphatidylserine, sphingomyelin, phosphatidic acid, palmitate, arachidonate, and auto-oxidized arachidonate had no effect on EDR. Concentrations (10 ,uM) of lysolecithin, lyso-platelet activating factor, and sphingosine significantly suppressed endotheliumdependent relaxation. Native LDL (100 ,ug/ml incubation buffer) containing only small amounts of lysophosphatidylcholine exerted no effect on EDR. In contrast, LDL preparations oxidatively modified by exposure to cultured endothelial cells or copper inhibited EDR. When modified LDL was depleted of its lysolecithin by treatment with a selective phospholipase B (lysolecithinase), the inhibitory effects were attenuated. In contrast, native LDL accumulating lysolecithin under the influence of a phospholipase A2 (lecithinase) exerted inhibitory effects mimicking those of oxidized LDL. Lipids and lipoproteins had no effect on the responsiveness to nitroglycerin, an endothelium-independent vasodilator. We conclude that lysolecithin in oxidatively modified LDL contributes importantly to its vasomotor effects. (Circulation Research 1993;72:161-166

Lipoprotein-like Phospholipid Particles Inhibit the Smooth Muscle Cell Cytotoxicity of Lysophosphatidycholine and Platelet-Activating Factor

“…9 Matsuda and coworkers 31 reported that this effect was reversed by HDL and that HDL also reversed inhibition of endothelialderived relaxation caused by addition of LPC alone. Moreover, they demonstrated that HDL inhibited incorporation of radiolabelled LPC into cultured endothelial cells and stimulated the efflux of LPC from the cells into the culture medium.…”

“…5 Although less reactive than PAF, LPC markedly affects the function of inflammatory cells. 8 It also inhibits endothelial-dependent arterial relaxation 9 ; activates endothelial expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, 10 as well as endothelial release of platelet-derived growth factor and heparin-binding epidermal growth factor-like protein 11 ; stimulates the macrophage production of tumor necrosis factor-␣ 12 ; and promotes SMC proliferation. 13 These findings suggest that PAF and LPC accumulation during intimal oxidation of LDL may be involved in activation of the inflammatory process and SMC proliferation associated with the formation of fibrous and complicated atherosclerotic plaque.…”

Effects of chylomicrons and chylomicron remnants on endothelium-dependent relaxation of rat aorta

“…Inhibition of relaxation to A23187 by Ž oxidised LDL has been demonstrated in rabbit aorta Jacobs . et al, 1990;Mangin et al, 1993although Tanner et al Ž . 1991 found no significant effect in porcine coronary artery.…”

Molecular bases of copper and iron deficiency-associated dyslipidemia: a microarray analysis of the rat intestinal transcriptome

“…Phospholipase B (PhlpB) (or Lysolecithinase B) catalyzes the hydrolysis of lysolecithins to glycerophosphorilcholine and FA. Oxidized LDL lipoproteins, that play a pivotal role in the development of atherosclerosis, contain lysolecithins that also cause the alteration of the vasal tone by impairing the endothelium-dependent relaxation [12]. On the other hand, lysolecithin concentration may significantly increase in the atherosclerotic arterial walls, and its cytotoxicity at high concentration may contribute to the cell death observed in the atheromatous lesions.…”