Takayoshi Ichikawa

Coexisting type III hyperlipoproteinemia and familial hypercholesterolemia: A case report

A 39-year-old man presented with type III hyperlipoproteinemia in association with heterozygous familial hypercholesterolemia (FH). He had extensive tuberous xanthomas over the knees and elbows and xanthomas in the Achilles tendons. He also had palmar xanthomas. He exhibited severe hypercholesterolemia and hypertriglyceridemia. This patient was heterozygous for FH, as evidenced by low low-density lipoprotein (LDL) receptor function on lymphocytes, and had type III hyperlipoproteinemia, as determined by apolipoprotein (apo) E phenotype 2/2 in isoelectric focusing of the E isoproteins and the presence of a broad beta band on electrophoresis. Because therapy consisting of diet restrictions and lipid-lowering agents such as clinofibrate and niceritrol did not decrease serum total cholesterol ([TC] 15.26 mmol/L) and triglyceride ([TG] 10.79 mmol/L) levels effectively, the patient underwent plasmapheresis once every 2 weeks using a dextran sulfate-cellulose column. Repeated plasmapheresis markedly reduced serum TC and TG and induced complete regression of the palmar xanthoma after 6 months. The severity of tuberous xanthomas on the knees and elbows was reduced after 2.5 years. After plasmapheresis, TC decreased to 1.94 mmol/L from 10.40 mmol/L and TG decreased to 0.33 mmol/L from 7.90 mmol/L. Plasmapheresis performed with a dextran sulfate-cellulose column was highly effective in removing the lipoprotein-remnant particles in this patient, leading to generalized improvement in the lipoprotein profile.

Changes of HDL subfraction concentration and particle size by intralipid in vivo.

The effects of the artificial triglyceride-phospholipid emulsion (10% intralipid) on HDL subfraction were studied in vivo. After a 14-h fast, subjects received intralipid via a 4-h infusion. Serum lipoproteins were analyzed before and at 4 and 6 h after the start of the infusion. At 4-h the following acute changes by infusion were observed. Triglyceride, phospholipid, free cholesterol, and esterified cholesterol in chylomicrons and VLDL increased. HDL2 as well as triglyceride, phospholipid, free cholesterol and protein within the HDL2 increased, while HDL3 decreased. An increase in HDL3 triglyceride was observed. The masses of apo A-I and A-II in the HDL2 density interval rose while these parameters fell in HDL3. There were decreases of apo C-II and C-III in the HDL subfractions and elevations in chylomicrons and VLDL. The particle size of the HDL subfractions increased. However, most of these acute changes at 4 h tended to disappear by 6 h. These results suggest that there is exchange of lipids and reversible transfer of apo C-II and C-III between HDL subfractions and intralipid, and conversion of HDL3 to HDL2 followed by the reverse conversion of HDL2 to HDL3 as the synthetic emulsion is cleared from the plasma.

Assessment of functional low-density-lipoprotein receptors on lymphocytes by a simplified method using culture medium with lipoprotein-free fetal calf serum and pravastatin

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