Regulation of plasma lipid transfer by the high-density lipoproteins

Mechanisms that regulate the activity of the plasma cholesteryl ester transfer protein (lipid protein transfer-I) are poorly understood. We have examined the role of endogenous regulators of the lipid transfer process, in particular the plasma high-density lipoproteins (HDLs), in both humans and two species previously reported to be devoid of cholesteryl ester transfer activity, the rat and the pig. Chromatography of d greater than 1.21 g/ml plasma on phenyl-Sepharose either enhanced (human) lipid transfer activity or unmasked (rat and pig) a nearly completely suppressed lipid transfer activity. The HDLs (either native or delipidated) were shown to be a rich source of a plasma lipid transfer inhibitor protein. Partial purification of the HDL-derived lipid transfer inhibitor protein was achieved by sequential chromatography on phenyl- and DEAE-Sepharose. Additional analysis of plasma from patients with very low (Tangier disease), normal, or very high levels of HDL cholesterol (hyperalphalipoproteinemia) revealed a significant inverse correlation between plasma cholesteryl ester transfer activity and the subjects HDL cholesterol level. These results suggest that circulating levels of the plasma high density lipoproteins may be an important determinant of plasma cholesteryl ester transfer activity, through the function of the HDL-derived lipid transfer inhibitor protein.