HDL biology
Analbuminemic patients show elevated CETP activity toward LDL, likely driven by lipoprotein-bound free fatty acids (Arterioscler Thromb Vasc Biol 1996)
Original title: Increased cholesteryl ester transfer activity in plasma from analbuminemic patients
Endogenous cholesterol esterification, phospholipid transfer, and cholesteryl ester transfer activities were measured in plasma from three analbuminemic patients and five controls, since analbuminemia is associated with high LDL and low HDL cholesterol. Endogenous cholesterol esterification and phospholipid transfer rates were unaffected, but transfer of radiolabeled cholesteryl esters from HDL to apoB-containing lipoproteins was consistently higher in analbuminemic plasma (473.6% versus 227.5% per hour per mL, P=.036), driven specifically by increased transfer toward LDL rather than triglyceride-rich lipoproteins. CETP mass was higher in analbuminemic patients but did not reach significance (5.18 versus 3.13 mg/L, P=.07). Since nonesterified fatty acids (NEFA) were elevated in analbuminemic lipoproteins, supplementing plasma with fatty acid-poor albumin reduced CETP activity significantly more in analbuminemic than in control plasma, supporting a role for lipoprotein-bound NEFA in driving the elevated CETP activity that shifts cholesteryl esters from HDL toward proatherogenic apoB-containing lipoproteins.
Original 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% x h(-1) x mL(-1) versus 227.5+/-84.0% x h(-1) x 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.