Advertisement

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

  • Per Tornvall
    Correspondence
    Correspondence to: Dr. Per Tornvall, King Gustaf V Research Institute, P.O. Box 6004, S-104 01 Stockholm, Sweden.
    Affiliations
    King Gustaf V Research Institute, Karolinska Institute and Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden
    Search for articles by this author
  • Anders Hamsten
    Affiliations
    King Gustaf V Research Institute, Karolinska Institute and Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden
    Search for articles by this author
  • Lars A. Carlson
    Affiliations
    King Gustaf V Research Institute, Karolinska Institute and Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Reardon M.F.
        • Fidge N.H.
        • Nestel P.J.
        Catabolism of very low density lipoprotein B apoprotein in man.
        J. Clin. Invest. 1978; 61: 850
        • Shepherd J.
        • Packard C.J.
        Apolipoprotein B metabolism in man.
        in: Holm G. Björkholm M. Biology of vascular disease. 3rd edn. Acta Med. Scand. Suppl.715. 1986: 61
        • Barenholz Y.
        • Olivecrona T.
        In vitro production of human plasma low density lipoprotein-like particles.
        J. Biol. Chem. 1979; 254: 6079
        • Carlson L.A.
        • Böttiger L.E.
        Risk factors for ischaemic heart disease in men and women.
        Acta Med. Scand. 1985; 218: 207
        • Åberg H.
        • Lithell H.
        • Selinus I.
        • Hedstrand H.
        Serum triglycerides are a risk factor for myocardial infarction but not for angina pectoris.
        Atherosclerosis. 1985; 54: 89
        • Boberg J.
        • Carlson L.A.
        • Freyschuss U.
        • Lassers B.W.
        • Wahlqvist M.L.
        Splanchnic secretion rates of plasma triglycerides and total and splanchnic turnover of plasma free fatty acids in men with normo- and hypertriglyceridemia.
        Eur. J. Clin. Invest. 1972; 2: 454
        • Grundy S.M.
        • Mok H.Y.I.
        • Zech L.
        • Steinberg D.
        • Berman B.
        Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia.
        J. Clin. Invest. 1979; 63: 1274
        • Eisenberg S.
        • Gavish D.
        • Oschry Y.
        • Fainaru M.
        • Deckelbaum R.J.
        Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment.
        J. Clin. Invest. 1984; 74: 470
        • Nestel P.
        • Billington T.
        • Tada N.
        • Nugent P.
        • Fidge N.
        Heterogeneity of very-low-density lipoprotein metabolism in hyperlipidemic subjects.
        Metabolism. 1983; 32: 810
        • Gianturco S.H.
        • Gotto Jr., A.M.
        • Bradley W.A.
        Hypertriglyceridemia: Lipoprotein receptors and atherosclerosis.
        Adv. Exp. Med. 1985; 183: 47
        • Tornvall P.
        • Carlson L.A.
        In vitro lipolysis of small very low density lipoproteins from human plasma. Dependence of characteristics of endproducts on the serum triglyceride concentration.
        J. Intern. Med. 1989; 225: 359
        • Carlson K.
        Lipoprotein fractionation.
        J. Clin. Pathol. 1973; 26/5: 32
        • Noble R.P.
        Electrophoretic separation of plasma lipoproteins in agarose gel.
        J. Lipid Res. 1968; 9: 693
        • Redgrave T.G.
        • Carlson L.A.
        Changes in plasma very low density and low density lipoprotein content, composition, and size after a fatty meal in normo- and hypertriglyceridemic man.
        J. Lipid. Res. 1979; 20: 217
        • Redgrave T.G.
        • Roberts D.C.K.
        • West C.E.
        Separation of plasma lipoproteins by density-gradient ultracentrifugation.
        Anal. Biochem. 1975; 65: 42
        • Bengtsson-Olivecrona G.
        • Olivecrona T.
        Binding of active and inactive forms of lipoprotein lipase to heparin. Effects of pH.
        Biochem. J. 1985; 226: 409
        • Carlson L.A.
        Extraction of lipids from human whole serum and lipoproteins and from rat liver tissue with methylene chloride-methanol: a comparison with extraction with chloroform methanol.
        Clin. Chim. Acta. 1985; 149: 89
        • Carlson L.A.
        • Holmquist L.
        Concentrations of apolipoproteins B, C-I, C-II, C-III and E in sera from normal men and their relation to serum lipoprotein levels.
        Clin. Chim. Acta. 1982; 124: 163
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the Folin phenol reagent.
        J. Biol. Chem. 1951; 193: 265
        • Holmqvist L.
        • Carlson K.
        • Carlson L.A.
        Comparison between the use of isopropanol and tetramethylurea for the solubilisation and quantitation of human serum very low density apolipoproteins.
        Anal. Biochem. 1978; 88: 457
        • Miller K.W.
        • Small D.M.
        Structure of triglyceride-rich lipoproteins: an analysis of core and surface phases.
        in: Gotto Jr., A.M. Plasma Lipoproteins. Elsevier Science Publishers BV, Amsterdam1987: 1
        • Chung B.H.
        • Cone J.T.
        • Segrest J.P.
        Defective in vitro lipolysis of type IV hyperlipidemic human plasma by purified milk lipoprotein lipase. Studies by single vertical spin centrifugation.
        J. Biol. Chem. 1982; 267/13: 7472
        • Oschry Y.
        • Olivecrona T.
        • Deckelbaum R.J.
        • Eisenberg S.
        Is hypertriglyceridemic very low density lipoprotein a precursor of normal low density lipoprotein?.
        J. Lipid Res. 1985; 26: 158
        • Eisenberg S.
        Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters.
        J. Lipid Res. 1985; 26: 487
        • Poapst M.
        • Reardon M.
        • Steiner G.
        Relative contribution of triglyceride-rich lipoprotein particle size and number to plasma triglyceride concentration.
        Arteriosclerosis. 1985; 4/5: 381
        • Gianturco S.H.
        • Lin A.H.-Y.
        • Hwang S.-L.C.
        • Young J.
        • Brown S.A.
        • Via D.P.
        • Bradley W.A.
        Distinct murine macrophage receptor pathway for human triglyceride-rich lipoproteins.
        J. Clin. Invest. 1988; 82: 1633