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LDL physical and chemical properties in familial combined hyperlipidemia
J E Hokanson1, R M Krauss, J J Albers
1Department of Medicine, University of Washington, Seattle 98195, USA.
Insights
Familial combined hyperlipidemia (FCHL) patients have smaller, denser LDL particles with less cholesterol and phospholipid. These LDL particle differences persist even when triglyceride levels are reduced, suggesting they are independent of triglyceride levels.
Area of Science:
- Lipid Metabolism
- Cardiovascular Disease Research
- Atherosclerosis Pathophysiology
Background:
- Familial combined hyperlipidemia (FCHL) is a common genetic dyslipidemia characterized by elevated triglycerides and/or cholesterol and increased apolipoprotein B (apoB).
- Small, dense low-density lipoprotein (LDL) particles are associated with hypertriglyceridemia, but their persistence in FCHL patients post-triglyceride reduction suggests other contributing factors.
Purpose of the Study:
- To investigate potential differences in the distribution and chemical composition of LDL species between FCHL patients and normolipidemic controls.
- To determine if observed LDL particle characteristics in FCHL are solely dependent on plasma triglyceride levels.
Main Methods:
- Characterization of LDL species using analytic ultracentrifugation and gradient gel electrophoresis.
- Separation of LDL fractions by equilibrium density gradient ultracentrifugation.
- Analysis of LDL particle size, density, flotation rate, and chemical composition (cholesterol, cholesteryl ester, phospholipid, triglyceride).
Main Results:
- FCHL patients exhibited a predominant LDL species with a lower flotation rate (S0f 4.7), higher density (1.041 g/mL), and smaller diameter (250 A) compared to controls (S0f 6.3, density 1.037 g/mL, diameter 262 A).
- Across all LDL fractions, FCHL patients consistently showed smaller particle diameters than control subjects.
- LDL particles from FCHL patients contained significantly less free cholesterol, cholesteryl ester, and phospholipid, with no difference in triglyceride content per particle.
Conclusions:
- LDL particles in FCHL patients are intrinsically smaller and denser, with reduced cholesterol and phospholipid content, compared to normolipidemic individuals.
- These distinct LDL particle characteristics in FCHL appear to be largely independent of plasma triglyceride levels.
- The findings suggest a unique LDL subspecies profile in FCHL that warrants further investigation regarding its role in cardiovascular risk.
Abstract:
Familial combined hyperlipidemia (FCHL) is characterized by elevations of triglyceride and/or cholesterol within families and an elevation in apoB. Although small dense LDL has been consistently associated with hypertriglyceridemia, small dense LDL persists despite reductions in triglyceride after treatment with gemfibrozil in FCHL. The current study evaluated potential differences in the distribution and chemical composition of LDL species in patients with FCHL and normolipidemic control subjects. LDL from FCHL patients was characterized by a relative abundance of a discrete LDL species with a mean peak analytic ultracentrifuge flotation rate (S0f) of 4.7 +/- 0.5 (SEM), a density of 1.041 +/- 0.001 g/mL, and a particle diameter of 250 +/- 1 A as assessed by gradient gel electrophoresis. The major LDL species in the control subjects had a higher mean S0f rate (6.3 +/- 0.4), was more buoyant (density, 1.037 +/- 0.001 g/mL), and was larger (diameter, 262 +/- 2 A). In addition, in a series of six LDL fractions separated by equilibrium density gradient ultracentrifugation, particle diameters were significantly smaller in all fractions from FCHL patients compared with those from control subjects. LDL particles from patients contained less free cholesterol, cholesteryl ester, and phospholipid than LDL from control subjects. The amount of triglyceride per LDL particle, however, did not differ between FCHL patients and control subjects. Differences in flotation rate and mass of the major LDL species between patients and control subjects could not be fully accounted for by differences in plasma triglyceride levels. Thus, LDL particles from FCHL patients are smaller and more dense with less cholesterol and phospholipid. Many of these differences appear to be independent of plasma triglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)