Advertisement

Estradiol fatty acid esterification is increased in high density lipoprotein subclass 3 isolated from hypertriglyceridemic subjects

      Abstract

      Estrogen fatty acid esters are potent lipophilic estrogens transported exclusively in lipoproteins. They are formed in HDL in a reaction catalyzed by LCAT which is considered a prerequisite for their antioxidative action. Our previous studies in normotriglyceridemic (NTG) individuals demonstrated that estradiol (E2) esterification occurred mainly in HDL3 causing accumulation of esterified, but not of unesterified E2 in the lipoprotein particles. Using HDL obtained from hypertriglyceridemic (HTG) patients, we now investigated the effect of altered HDL composition on E2 esterification. Ultracentrifugally isolated HDL2 and HDL3 from NTG- and HTG-males were incubated in an in vitro model system with radioactive and with supraphysiological concentrations of non-radioactive E2 with and without exogenous LCAT. After purification, copper-induced oxidation of HDL was measured by monitoring conjugated diene formation. The results demonstrated that (i) E2 esterification occurring mainly in HDL3 was significantly more efficient in HTG-HDL3 compared to NTG-HDL3, (ii) triglyceride content in HDL3 correlated positively with E2 esterification rate, and (iii) addition of both exogenous LCAT and E2 into the incubation prolonged lag time of HDL3 oxidation. Thus, HDL composition regulates LCAT-facilitated E2 esterification but the in vivo role of this finding can be verified only in experiments using physiological hormone concentrations.

      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

        • Lamarche B.
        • Despres J.P.
        • Moorjani S.
        • Cantin B.
        • Dagenais G.R.
        • Lupien P.J.
        Triglycerides and HDL-cholesterol as risk factors for ischemic heart disease. Results from the Quebec cardiovascular study.
        Atherosclerosis. 1996; 119: 235-245
        • Chang L.B.
        • Hopkins G.J.
        • Barter P.J.
        Particle size distribution of high density lipoproteins as a function of plasma triglyceride concentration in human subjects.
        Atherosclerosis. 1985; 56: 61-70
        • Lamarche B.
        • Rashid S.
        • Lewis G.F.
        HDL metabolism in hypertriglyceridemic states: an overview.
        Clin Chim Acta. 1999; 286: 145-161
        • Barrans A.
        • Collet X.
        • Barbaras R.
        • et al.
        Hepatic lipase induces the formation of pre-beta 1 high density lipoprotein (HDL) from triacylglycerol-rich HDL2. A study comparing liver perfusion to in vitro incubation with lipases.
        J Biol Chem. 1994; 269: 11572-11577
        • Clay M.A.
        • Newnham H.H.
        • Forte T.M.
        • Barter P.I.
        Cholesteryl ester transfer protein and hepatic lipase activity promote shedding of apoA–I from HDL and subsequent formation of discoidal HDL.
        Biochim Biophys Acta. 1992; 1124: 52-58
        • Lewis G.F.
        • Steiner G.
        Hypertriglyceridemia and its metabolic consequences as a risk factor for atherosclerotic cardiovascular disease in non-insulin-dependent diabetes mellitus.
        Diabetes Metab Rev. 1996; 12: 37-56
        • Rye K.A.
        • Jauhiainen M.
        • Barter P.J.
        • Ehnholm C.
        Triglyceride-enrichment of high density lipoproteins enhances their remodelling by phospholipid transfer protein.
        J Lipid Res. 1998; 39: 613-622
        • Fielding C.J.
        • Fielding P.E.
        Purification and substrate specificity of lecithin-cholesterol acyl transferase from human plasma.
        FEBS Lett. 1971; 15: 355-358
        • Barter P.J.
        • Rye K.A.
        Molecular mechanisms of reverse cholesterol transport.
        Curr Opin Lipidol. 1996; 7: 82-87
        • Saku K.
        • Ahmad M.
        • Glas-Greenwalt P.
        • Kashyap M.L.
        Activation of fibrinolysis by apolipoproteins of high density lipoproteins in man.
        Thromb Res. 1985; 39: 1-8
        • Cockerill G.W.
        • Rye K.A.
        • Gamble J.R.
        • Vadas M.A.
        • Barter P.J.
        High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules.
        Arterioscler Thromb Vasc Biol. 1995; 15: 1987-1994
        • Mackness M.I.
        • Durrington P.N.
        HDL, its enzymes and its potential to influence lipid peroxidation.
        Atherosclerosis. 1995; 115: 243-253
        • Banka C.L.
        High density lipoprotein and lipoprotein oxidation.
        Curr Opin Lipidol. 1996; 7: 139-142
        • Francis G.A.
        High density lipoprotein oxidation: in vitro susceptibility and potential in vivo consequences.
        Biochim Biophys Acta. 2000; 1483: 217-235
        • Mendelsohn M.E.
        Protective effects of estrogen on the cardiovascular system.
        Am J Cardiol. 2002; 89 (Discussion 17E-18E): 12E-17E
        • Höckerstedt A.
        • Tikkanen M.J.
        • Jauhiainen M.
        LCAT facilitates transacylation of 17 beta-estradiol in the presence of HDL3 subfraction.
        J Lipid Res. 2002; 43: 392-397
        • Kanji S.S.
        • Kuohung W.
        • Labaree D.C.
        • Hochberg R.B.
        Regiospecific esterification of estrogens by lecithin:cholesterol acyltransferase.
        J Clin Endocrinol Metab. 1999; 84: 2481-2488
        • Shwaery G.T.
        • Vita J.A.
        • Keaney Jr., J.F.
        Antioxidant protection of LDL by physiological concentrations of 17 beta-estradiol. Requirement for estradiol modification.
        Circulation. 1997; 95: 1378-1385
        • Tikkanen M.J.
        • Vihma V.
        • Höckerstedt A.
        • Jauhiainen M.
        • Helisten H.
        • Kaamanen M.
        Lipophilic oestrogen derivatives contained in lipoprotein particles.
        Acta Physiol Scand. 2002; 176: 117-121
        • Hochberg R.B.
        Biological esterification of steroids.
        Endocr Rev. 1998; 19: 331-348
        • Tang M.
        • Abplanalp W.
        • Subbiah M.T.
        Association of estrogens with human plasma lipoproteins: studies using estradiol-17beta and its hydrophobic derivative.
        J Lab Clin Med. 1997; 129: 447-452
        • Havel R.J.
        • Eder H.A.
        • Bragdon J.H.
        The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.
        J Clin Invest. 1955; 34: 1345-1353
        • Lowry O.H.
        • Rosenbrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the Folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Jauhiainen M.
        • Dolphin P.J.
        Human plasma lecithin-cholesterol acyltransferase. An elucidation of the catalytic mechanism.
        J Biol Chem. 1986; 261: 7032-7043
        • Zhou G.Y.
        • Jauhiainen M.
        • Stevenson K.
        • Dolphin P.J.
        Human plasma lecithin:cholesterol acyltransferase. Preparation and use of immobilized p-aminophenylarsenoxide as a catalytic site-directed covalent ligand in enzyme purification.
        J Chromatogr. 1991; 568: 69-83
        • Vihma V.
        • Tiitinen A.
        • Ylikorkala O.
        • Tikkanen M.J.
        Quantitative determination of estradiol fatty acid esters in lipoprotein fractions in human blood.
        J Clin Endocrinol Metab. 2003; 88: 2552-2555
        • Esterbauer H.
        • Striegl G.
        • Puhl H.
        • Rotheneder M.
        Continuous monitoring of in vitro oxidation of human low density lipoprotein.
        Free Radic Res Commun. 1989; 6: 67-75
        • Helisten H.
        • Höckerstedt A.
        • Wähälä K.
        • et al.
        Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid esters in low-density lipoprotein particles.
        J Clin Endocrinol Metab. 2001; 86: 1294-1300
        • Vohl M.C.
        • Neville T.A.
        • Kumarathasan R.
        • Braschi S.
        • Sparks D.L.
        A novel lecithin-cholesterol acyltransferase antioxidant activity prevents the formation of oxidized lipids during lipoprotein oxidation.
        Biochemistry. 1999; 38: 5976-5981
        • Goyal J.
        • Wang K.
        • Liu M.
        • Subbaiah P.V.
        Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.
        J Biol Chem. 1997; 272: 16231-16239
        • Dolphin P.J.
        Rosseneu M. Structure and function of apolipoproteins. CRC Press, 1992: 295-362
        • Pinon J.C.
        • Bridoux A.M.
        • Laudat M.H.
        Initial rate of cholesterol esterification association with high density lipoproteins in human plasma.
        J Lipid Res. 1980; 21: 406-414
        • Settasatian N.
        • Duong M.
        • Curtiss L.K.
        • et al.
        The mechanism of the remodeling of high density lipoproteins by phospholipid transfer protein.
        J Biol Chem. 2001; 276: 26898-26905
        • Frank P.G.
        • Bergeron J.
        • Emmanuel F.
        • et al.
        Deletion of central alpha-helices in human apolipoprotein A–I: effect on phospholipid association.
        Biochemistry. 1997; 36: 1798-1806
        • Roosbeek S.
        • Vanloo B.
        • Duverger N.
        • et al.
        Three arginine residues in apolipoprotein A–I are critical for activation of lecithin:cholesterol acyltransferase.
        J Lipid Res. 2001; 42: 31-40