Down-regulation of hepatic high-density lipoprotein receptor, SR-B1, in nephrotic syndrome

Background. Nephrotic syndrome (NS) is a prototype of acquired hypercholest erolemia. Hepatic synthesis and removal of cholesterol play major roles in the regulation of plasma concentration of this sterol. Low-density lipoprot ein (LDL) and high-density lipoprotein (HDL) particles are the primary vehi cles for cholesterol transport to the liver. We have recently demonstrated that NS results in acquired hepatic LDL receptor deficiency in rats. This s tudy was undertaken to determine the effect of NS on hepatic expression of the newly discovered, long-sought HDL receptor. Methods. Hepatic HDL receptor and apolipoprotein A-I (apo A-I) expressions were studied in rats with puromycin-induced NS. The results were compared w ith those obtained in placebo-treated, normal controls. Results. The NS group exhibited a marked reduction in hepatic tissue HDL re ceptor protein abundance when compared with the control group. In contrast, hepatic HDL receptor mRNA abundance in the NS group was similar to that of the control group. As expected, the NS group showed a marked increase in h epatic apo A-I mRNA abundance. Conclusions. The study explored the effect of experimental NS on hepatic HD L receptor expression, and the results revealed a marked down-regulation of HDL receptor in rats with NS. In contrast, hepatic expression of Apo A-I, the principal protein constituent of HDL, was markedly increased in NS rats . The HDL receptor deficiency shown here can potentially limit the efficien cy of HDL as the primary vehicle for reverse cholesterol transport in NS.