Abnormalities of composition and of in vitro lipolysis products of human small very low density lipoproteins in hypertriglyceridemia

  • Per Tornvall
    Correspondence to: Dr. Per Tornvall, King Gustaf V Research Institute, P.O. Box 6004, S-104 01 Stockholm, Sweden.
    King Gustaf V Research Institute, Karolinska Institute and Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden
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  • Anders Hamsten
    King Gustaf V Research Institute, Karolinska Institute and Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden
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  • Lars A. Carlson
    King Gustaf V Research Institute, Karolinska Institute and Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden
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      Small (Sf 20–100) very low density lipoprotein (VLDL) particles were prepared by density gradient ultracentrifugation of plasma from normolipidemic and type IV hypertriglyceridemic post-infarction patients and healthy controls. The small VLDL separated from the plasma of severely hypertriglyceridemic post-infarction patients were found to contain twice the amount of cholesteryl esters per particle, compared with small VLDL from normolipidemic patients and healthy controls. There was a linear increase in the percentage of cholesterol that was esterified in the small VLDL with the serum VLDL triglyceride concentration (r = 0.66). When incubated for two hours with bovine lipoprotein lipase in excess and bovine albumin as a free fatty acid acceptor at one and the same triglyceride concentration in the medium, the end-product isolated by ultracentrifugation varied as a function of the serum VLDL triglyceride level. The amount of glyceride-glycerol recovered after two hours of incubation with lipoprotein lipase was 13.3 ± 1.3% (mean ± SEM) of the initial values and did not correlate with the VLDL triglyceride level. With rising serum VLDL triglyceride concentration, the product isolated in the low density lipoprotein (LDL) density region (1.006 < d < 1.063 kg/1) contained more total cholesterol and phospholipids. The linear correlation coefficients for these relations were 0.65 and 0.58 for cholesterol and phospholipids respectively. The ratio of total cholesterol to insoluble protein in the LDL density range after lipolysis rose with increasing serum VLDL triglyceride level (r = 0.68). The end-product was further characterized by density gradient ultracentrifugation of the incubate. In vitro LDL derived by lipolysis of normolipidemic small VLDL was denser than in vitro LDL of hypertriglyceridemic small VLDL. A significant relation was found between the percentage of cholesteryl esters of total cholesterol in the substrate and the relative amount of total cholesterol recovered in the LDL density fraction after lipolysis (r = 0.69). We suggest that the enrichment with cholesteryl esters of small VLDL from type IV hypertriglyceridemic patients is caused by lipid transfer from LDL and high density lipoprotein (HDL) and that the change in VLDL particle composition influences the precursor-product relationship to LDL.


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