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Characterization of high density lipoproteins from patients with severe hypertriglyceridemia
Insights
Severe hypertriglyceridemia alters high density lipoproteins (HDL). These HDL particles are larger, denser, and contain more triglycerides, explaining their lower cholesterol content in patients.
Area of Science:
- Lipid Metabolism and Cardiovascular Health
- Biochemistry of Lipoproteins
Background:
- Severe hypertriglyceridemia is associated with altered lipoprotein profiles.
- Understanding high-density lipoprotein (HDL) composition is crucial for cardiovascular risk assessment.
Purpose of the Study:
- To characterize the physical and chemical properties of HDL in subjects with severe hypertriglyceridemia.
- To investigate the impact of hypertriglyceridemia on HDL subpopulations and their lipid/apoprotein content.
Main Methods:
- Isolation of HDL using zonal ultracentrifugation from 6 hypertriglyceridemic subjects.
- Analysis of HDL particle size, density, triglyceride, cholesteryl ester, and apoprotein C content.
- Comparison with HDL from normolipidemic control subjects.
Main Results:
- The predominant HDL subpopulation in hypertriglyceridemic subjects was denser (peak mean density 1.153 g/ml) than normal HDL3.
- These HDL particles were significantly larger (mean diameter 8.4 nm) and enriched in triacylglycerols (mass ratio 4.00-5.22) compared to controls (0.41).
- A depletion of cholesteryl esters and apoprotein C was observed in the HDL of hypertriglyceridemic patients.
Conclusions:
- Severe hypertriglyceridemia shifts HDL composition towards larger, denser particles with increased triglyceride content.
- This altered composition, particularly the enrichment in triglycerides, contributes to the reduced cholesterol levels observed in HDL from these patients.
- Findings highlight specific structural and compositional changes in HDL associated with severe hypertriglyceridemia.
Abstract:
High density lipoproteins (HDL) were isolated by zonal ultracentrifugation from 6 subjects with severe hypertriglyceridemia. Four subjects had familial endogenous hypertriglyceridemia with fasting chylomicronemia; 2 subjects were non-insulin-dependent diabetics. Plasma triglycerides ranged from 920 to 5440 mg/dl and HDL-cholesterol from 12 to 23 mg/dl. The major HDL from these hypertriglyceridemic subjects had a peak mean density of 1.153 g/ml as compared to 1.140 g/ml for HDL3 from normal subjects. None of the subjects had significant amounts of HDL corresponding to normal HDL2. The major subpopulation of hypertriglyceridemic HDL had a mean diameter of 8.4 +/- 0.1 nm (range 7.6-9.0 nm). The HDL were enriched in triacylglycerols and depleted in cholesteryl esters and the C apoproteins as compared to control HDL3. The mass ratio of triacylglycerols to cholesteryl esters ranged from 4.00 to 5.22 for the patients versus 0.41 for normal HDL3. The increased content of triacylglycerols partially explains the decreased amount of cholesterol associated with these hypertriglyceridemic HDL.