Enhanced cholesteryl ester transfer protein activities and abnormalities of high density lipoproteins in familial hypercholesterolemia.
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 greater than 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 less than d less than 1.21 g/ml) to LDL (1.019 less than d less than 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 greater than 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d greater than 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p less than 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = -0.334, p less than 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.
Inazu
A
A
Second Department of Internal Medicine, School of Medicine, University of Kanazawa, Japan.
Koizumi
J
J
Mabuchi
H
H
Kajinami
K
K
Takeda
R
R
D000328:Adult; D001053:Apolipoproteins / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins