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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:441-449.)
© 1996 American Heart Association, Inc.

Articles

Increased Cholesteryl Ester Transfer Activity in Plasma From Analbuminemic Patients

Sylvie Braschi; Laurent Lagrost; Emmanuel Florentin; Claude Martin; Anne Athias; Philippe Gambert; Michel Krempf; Christian Lallemant; Bernard Jacotot

From the Service de Médecine V and INSERM U391, Hôpital Henri Mondor (S.B., C.M., B.J.), Créteil; the Laboratoire de Biochimie des Lipoprotéines, INSERM CJF 93-10, Faculté de Médecine (L.L., E.F., A.A., P.G., C.L.), Dijon; and the Service d'Endocrinologie, Hôtel Dieu (M.K.), Nantes, France.

Correspondence to Laurent Lagrost, Laboratoire de Biochimie Médicale, Hôpital du Bocage, 21034 Dijon, France.

Abstract Hypercholesterolemia associated with analbuminemia, an inherited disease manifesting low plasma albumin concentration, is characterized by enhanced LDL cholesterol levels and reduced HDL cholesterol levels. In addition, compared with normal counterparts, the esterified cholesterol:triglyceride ratio tends to be higher in analbuminemic apoB-containing lipoproteins and lower in analbuminemic HDL. The aim of the present study was to investigate the mechanism that may account for the association of a hypoalbuminemic state with alterations in the concentration and composition of plasma lipoprotein fractions. To this end, endogenous cholesterol esterification activity, phospholipid transfer activity, and cholesteryl ester transfer activity were measured in total plasma from three analbuminemic patients and five control subjects. Whereas endogenous cholesterol esterification and phospholipid transfer rates were not significantly affected in analbuminemia, the transfer of radiolabeled cholesteryl esters from HDL toward apoB-containing lipoproteins was constantly higher in analbuminemic plasmas than in normal control plasma (473.6±107.3%·h^-1·mL^-1 versus 227.5±84.0%·h^-1·mL^-1, respectively; P=.036). The rise in cholesteryl ester transfer protein (CETP) activity in analbuminemic plasma was due to a significant increase in the transfer of radiolabeled cholesteryl esters toward LDL but not toward the triglyceride-rich lipoproteins. The CETP mass was higher in analbuminemic patients than in control subjects, but the difference did not reach the significance level (5.18±0.82 mg/L versus 3.13±1.19 mg/L, respectively; P=.07). Since abnormally elevated nonesterified fatty acid (NEFA) levels were shown to be associated with analbuminemic lipoproteins, mostly LDL, the direct role of lipoprotein-bound NEFA in enhancing CETP activity was suspected. In support of this view, supplementation of total plasmas with fatty acid–poor albumin was shown to reduce CETP activity to a significantly greater extent in analbuminemic plasmas than in normal control plasma. It is concluded that hyperlipidemia associated with the hypoalbuminemic state can relate, at least in part, to the combined effect of CETP and NEFA in promoting the transfer of cholesteryl esters from the antiatherogenic HDL toward the proatherogenic apoB-containing lipoproteins.

Key Words: lipoprotein • cholesteryl ester transfer protein • hypoalbuminemia • triglyceride • cholesteryl ester

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