Familial lipoprotein lipase deficiency: abnormal lipoproteins and defective metabolism of low density lipoproteins in cultured human skin fibroblasts.

Lipoproteins (chylomicrons + VLDL, VLDL, IDL, LDL and HDL) were separated from the plasma of 2 patients with primary, familial lipoprotein lipase deficiency. Chylomicrons were excessively enriched with cholesteryl esters. VLDL and IDL were of almost normal composition. LDL separated into 2 fractions LDL1 and LDL2, both triglyceride- and protein-rich and cholesteryl ester-poor. LDL2, the main LDL fraction, was denser and smaller than normal LDL. HDL3 was the only HDL population identified and was also triglyceride- and protein-rich and cholesteryl ester-poor. These observations indicate excessive triglyceride and cholesteryl ester transfer between chylomicrons and LDL and HDL. VLDL and its immediate catabolic product, IDL, seem to be spared the effects of the lipid transfer reaction. The biological reactivity of LDL1 and LDL2 was investigated in upregulated cultured human skin fibroblasts. Both exhibited defective specific binding to the LDL receptor and ineffective capacity to down-regulate sterol synthesis. These abnormalities were more pronounced with LDL3. The ineffective downregulation of sterol synthesis is most probably due to both the cholesterol content of the LDLs and their reduced binding to the LDL receptor. The defective binding of the LDLs to the receptor can be attributed to the abnormal composition of the lipoproteins and, to a lesser degree, reduced diameters (only LDL2). It is concluded that abnormal composition of LDL, in particular of lipid moieties, may change the affinity of the moiety of the lipoprotein towards the LDL receptor.