Abnormal acyltransferase activities and accelerated cholesteryl ester transfer in patients with nephrotic syndrome

Abstract

To determine the effects of the nephrotic syndrome (NS) on atherogenic risk, we studied the lipoprotein composition and the activities of lecithin-cholesterol acyltransferase (LCAT), lysolecithin acyltransferase (LAT), and cholesteryl ester transfer (CET) in the plasma of 11 NS patients and 10 control subjects. NS plasma had lower ratios of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and HDL 2 HDL 3 and an elevated free cholesterol (FC) to phosphatidyl choline (PC) ratio (1.09 ± 0.27 in NS and 0.72 ± 0.21 in controls, P < .02), all of which indicate an increased atherogenic potential. LCAT activity was normal in NS plasma when assayed with an exogenous substrate, but was 40% lower than in control plasma when assayed with the endogenous substrates. However, in vitro addition of serum albumin to NS plasma failed to normalize the LCAT activity. The LAT reaction, which is catalyzed by LCAT protein in the presence of LDL, was 60% to 80% higher in NS plasma, and consequently the ratio of LAT LCAT activities was increased twofold. CET activity was significantly increased (+160% of control), and this abnormality was attributable to changes in both the acceptor (very-low-density lipoprotein [VLDL] + LDL) and donor (HDL) lipoproteins and possibly in CET protein. These results suggest that the NS may increase the risk of atherosclerosis not only by adversely affecting the concentrations of lipoproteins, but also by altering their composition and function.