Effect of EPL on the Metabolism of Lipids in the Arterial Wall

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Intracellular accumulation of lipids, mainly of cholesteryl oleate, is the characteristic feature of the early fatty streak lesion in atherosclerosis. By the use of experimental models of fatty streak lesions, such as the cholesterol-fed rabbit, it has been shown that in situ synthesis can contribute as much as 50% of the cholesteryl oleate. Since in vitro studies showed that essential phospholipids (EPL) are able to influence the arterial lipid metabolism, EPL might be expected to reduce lipid accumulation or even to promote regression of fatty streaks. Therefore the effect of EPL on the metabolic turnover of lipids was studied using a new technique of perfusion of the intact rabbit aorta. Segments of the aortas were perfused in vitro under physiological conditions of temperature, blood flow and blood pressure. Two aspects of arterial metabolism were studied in the normal rabbit aorta: (1) the effect of EPL on synthesis of lipids during a one hour perfusion with 3H-acetate in normal rabbit plasma and (2) the effect of EPL on the efflux of previously endogenously synthesized lipids during a one hour perfusion with a buffer solution containing serum albumin as a fatty acid acceptor. The following results were obtained: 1) Following perfusion in the presence of EPL, the concentration of lysolecithin (LPC), phosphatidyl serine (PS) and phosphatidyl ethanolamine (PE) were significantly reduced. There were no changes in cholesterol or other lipid fractions. This suggests that the presence of a micellar suspension of the polar EPL in plasma may withdraw phospholipids from the arterial wall, especially those associated with the plasma membrane. 2) Perfusion in the presence of EPL caused a significant reduction in the incorporation of acetate into the free fatty acid (FFA) pool of the artery. In general the mean values for incorporation into other lipids were also lower, but did not reach statistical significance. EPL may reduce synthesis of FFA or reduce the amount of newly synthesized fatty acid in the arterial wall by favoring efflux. 3) The absolute rates of lipid synthesis as estimated from the specific activity of the free fatty acid pool did not differ significantly between the control and the EPL groups. 4) EPL was found to increase the mole fraction of lyso-lecithin (LPC) and cholesteryl esters (CE) metabolically labeled by the newly synthesized fatty acid. This result reveals that EPL caused more of the available FFA to be diverted into LPC and CE, although the incoporation of acetate into the FFA pool of the artery was reduced. 5) The newly synthesized fatty acids are removed from the artery by a buffer perfusion. This removal appears to be increased by the presence of EPL.