We have studied the lipoproteins, apolipoproteins, and postheparin lipase activities In an extended pedigree with familial hepatic lipase deficiency. A deficiency of hepatic lipase was found In three of five brothers and In one of their children. Trlglycerlde enrichment of low density and high density lipoproteins was Identified as the constitutive phenotype. 0-very low density lipoproteln was observed In hepatic llpase-deflclent subjects, but It was absent when the plasma trlglycerlde concentration was less than 1 mM/l. The hepatic llpase-deflclent subjects had normal or elevated low density lipoproteln cholesterol and high density lipoproteln cholesterol concentrations. Hyperprebetalipoprotelnemla, hyperbetallpoprotelnemla, and hyperalphallpoproteinemla were observed In both affected and unaffected family members. Compared with the unaffected family members, the hepatic lipase-deflclent subjects had no significant differences In very low density lipoproteln cholesterol, very low density lipoproteln trlglycerlde, or low density lipoproteln cholesterol. These observations are consistent with the presence of additional genes causing hyperilpIdemla In this family, independent of the deficiency of hepatic lipase. The role of HL in lipoprotein metabolism is only partly understood. 1 -» Postheparin plasma HL activity has been reported to be positively correlated with VLDL concentration and negatively correlated with HDL cholesterol concentration.2 -5 It is known that in vitro HL will hydrolyze HDL triglyceride and phospholipid. 6 Intermediate density lipoproteins (IDL) and low density lipoproteins (LDL) with a density between 1.019 and 1.045 have also been shown to be in vitro substrates of HL. 78 The inhibition of HL in vivo by infusion of anti-HL antibody into rats 9 ' 1011 and cynomolgous monkeys 12 has been found to result in the increase of HDL and IDL. However, there is no agreement on the temporal relationships of these changes and no consistent changes in IDL between species. In the study on the primate model, 12 VLDL triglyceride concentrations increased 60% to 300% after infusion of anti-HL antibody. These authors did not report whether the VLDL contained particles of /3 electrophoretic mobility.The discovery of familial HL deficiency 13 has provided an opportunity to investigate the role of HL in lipoprotein metabolism in humans. The proband and his brother were markedly hvpertriglyceridemic, with hyperprebetalipoproteinemia, /3-VLDL, normal or elevated concentrations of LDL cholesterol and HDL cholesterol, and elevated concentrations of LDL and HDL triglyceride and phospholipid. Recently another family with HL deficiency and virtually identical qualitative lipoprotein abnormalities has been described.14 The brothers studied in our laboratory have significant ischemic vascular disease and plasma apolipoprotein (apo) B levels approximately twice the normal level, 13 in contrast to the Scandinavian subjects, 14 who had no apparent ischemic vascular disease and normal levels of plasma apo B. The turnover of ...

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