Enhanced Cholesteryl Ester Transfer Protein Activities and Abnormalities of High Density Lipoproteins in Familial Hypercholesterolemia

 

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Summary

Cholesteryl ester transfer protein may play a role in the cholesteryl ester metabolism between high density lipoproteins (HDL) and apolipoprotein B-containing lipoproteins. To investigate relationship between HDL and cholesteryl ester transfer protein (CETP) activity in the development of atherosclerosis, the present study has focused on CETP activity in the patients with familial hypercholesterolemia (GH). HDL-C and HDL-C/apo A-I mass ratio in heterozygous FH were lower than those in normolipidemic controls. There was a 2-fold increase in total CETP activity in incubated FH serum compared with normolipidemic controls. Assays for CETP activity in the lipoprotein deficient serum (d > 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 < d < 1.21 g/ml) to LDL (1.019 < d < 1.060 g/ml). CETP activities in heterozygous FH (79±4 nmol/ml/h) was significantly higher than those in normolipidemic controls (54±6 nmol/ml/h). The increased total cholesteryl ester transfer mainly results from increased CETP activity in the d > 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d > 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p< 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = -0.334, p < 0.05). These results indicate that the enhanced CETP activities may contribute to increase risk for developing atherosclerosis in FH by changing the distribution of cholesteryl ester in serum lipoproteins.