Marked overproduction of low density lipoprotein apolipoprotein B in a subject with heterozygous familial hypercholesterolemia effect of portacaval shunting

Portacaval shunt has been shown to result in reduced plasma levels of cholesterol in subjects with familial hypercholesterolemia. To define better the effect of this procedure on lipoprotein metabolism, we measured the turnover of apolipoprotein B in very low density and low density lipoprotein in a subject with heterozygous familial hypercholesterolemia and hypertriglyceridemia before and after a portacaval shunt. Pre-shunt, total plasma cholesterol and low density lipoprotein cholesterol were 495.7 ±22.5 and 383 ±11.6 mg/dl (mean ± S.D.), respectively. Post-shunt, these levels fell to 286.0 ±8.3 and 226.0 ±23.4 mg/dl, respectively. Plasma triacylglycerol concentration was also reduced by surgery (279.8 ±49.3 vs. 55.2 ±8.4 mg/dl). The production of very low density lipoprotein apolipoprotein B was dramatically reduced after surgery (27.9 vs. 7.8 mg/kg/day). The secretion of triacylglycerol in very low density lipoproteins was similarly affected. During baseline, production of low density lipoprotein apolipoprotein B was markedly elevated (64.8 mg/kg/day) and 75% was secreted directly into plasma. Post-shunt, the production of low density lipoprotein decreased to a normal level (11.3 mg/kg per day). However, 31% of the LDL was still secreted directly into plasma. Pre-shunt, the fractional catabolic rate of low density lipoprotein apolipoprotein B was normal (0.57/day) in this subject with less than 50% of normal apolipoprotein B receptor activity. After surgery, concomitant with reduced lipoprotein production and plasma concentrations, the fractional catabolic rate fell to 0.19/day, a level compatible with the presence of reduced receptors. The data indicate that portacaval shunt can significantly reduce the flux of lipoproteins in subjects with hyperlipoproteinemia and that the liver is a major site of both production and catabolism of those lipoproteins.