Importance of Phospholipids in Cholesterol-Solubilizing Capacity of High-Density Lipoproteins

Abstract

Cholesterol (Ch) efflux from cells or deposits (such as the arterial wall and gallstones) is a primary goal of therapy. The removal of cholesterol requires several steps: first, it is desorbed from the membranes or from the surface of solid cholesterol; subsequently, the Ch diffuses into the unstirred water layer where several acceptors, such as albumin, lipoproteins, apolipoproteins and lecithin in monomeric form, can take it up. Phospholipids and in particular phosphatidylcholines (PC) are the physiological solubilizers of Ch and they are important constituents of high density lipoproteins (HDL). The presence of PC in the unstirred water layer is therefore important for cholesterol solubilization and transport. It is noteworthy that Ch solubility in water is higher than that of PC (10^-8 vs 10^-10 M) (Haberland and Reynolds 1973); consequently, Ch concentration in the unstirred water layer (UWL) is greater than that of PC. But the presence of PC in monomeric form or assembled in particles plays a key role in Ch solubilization (Rothblat and Phillips 1982). HDL bind some PC from sonicated dispersions introduced into the vein (Scherphof et al. 1978) or from mixed micelles, as in the commercial preparation Lipostabil. HDL are responsible for reverse Ch transport. Moreover, hydrophilic PC molecular species desorb more readily from membranes, since diunsaturated PC have a faster exchange rate (Robbins and Patton 1986). Recently, Nichols (1986) demonstrated that bile salts at concentrations in the range found in blood during the postprandial period bind to vesicles, reducing the stability of bilayer phospholipids and enhancing their transfer rate between the particles.