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Relationship between cholesteryl ester transfer activity and high density lipoprotein composition in hyperlipidemic
D L Sparks1, J Frohlich, A G Lacko
1Department of Pathology, University of British Columbia, Vancouver, Canada.
Atherosclerosis
|June 1, 1989
Summary
Cholesteryl ester transfer protein function is impaired in patients with lipid metabolism disorders. Reduced transfer to HDL3 may increase coronary heart disease risk in these individuals.
Area of Science:
- Lipid Metabolism
- Cardiovascular Disease Risk Factors
- Atherosclerosis Research
Background:
- Cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl esters between lipoproteins.
- Dysfunctional lipid metabolism is a known risk factor for cardiovascular diseases.
- Understanding CETP's role in various lipid disorders is crucial for risk stratification.
Purpose of the Study:
- To investigate cholesteryl ester transfer from HDL to plasma lipoproteins in patients with primary lipid metabolism disorders.
- To determine if altered lipid transfer correlates with specific lipoprotein profiles and vascular disease.
- To elucidate the role of CETP in the pathogenesis of coronary heart disease in dyslipidemic populations.
Main Methods:
- Assessed cholesteryl ester transfer from solid-phase bound HDL to endogenous plasma HDL, VLDL/LDL in 50 patients with lipid disorders and 27 controls.
- Utilized HDL subfractionation (HDL2, HDL3) to analyze differential lipid transfer.
- Correlated lipid transfer rates with plasma lipid levels and presence of vascular disease.
Main Results:
- Significantly reduced transfer to the plasma HDL pool was observed in familial hypercholesterolemia, familial combined hyperlipidemia, hypoalphalipoproteinemia, and dysbetalipoproteinemia.
- Lipid transfer to HDL3 was reduced in all patient groups; transfer to HDL2 increased in dysbetalipoproteinemia and familial hypertriglyceridemia.
- Increased transfer to LDL and VLDL was noted in dysbetalipoproteinemia and hypoalphalipoproteinemia.
- Reduced HDL transfer correlated with increased HDL-triglyceride and decreased HDL-cholesteryl esters.
- Decreased cholesteryl ester transfer to HDL3 was associated with vascular disease.
Conclusions:
- Impaired cholesteryl ester transfer to HDL, particularly HDL3, is evident in various primary lipid metabolism disorders.
- Altered HDL composition, characterized by increased triglycerides and decreased cholesteryl esters, is linked to reduced CETP function.
- Impaired CETP interaction with the HDL3 pool may be a contributing factor to coronary heart disease risk in patients with specific lipid abnormalities.