Download PDF
Int J Sports Med 2002; 23(7): 477-483
DOI: 10.1055/s-2002-35066
Physiology & Biochemistry

© Georg Thieme Verlag Stuttgart · New York

Combination of Estrogen Replacement and Exercise Protects Against HDL Oxidation in Post-Menopausal Women

J.  M.  Lawler1 , Z.  Hu1 , J.  S.  Green2 , S.  F.  Crouse2 , P.  W.  Grandjean3 , R.  G.  Bounds2
  • 1Department od Health and Kinesiology, Texas A&M University, Redox Biology and Cell Signaling Laboratory
  • 2Department od Health and Kinesiology, Texas A&M University, Applied Exercise Science Laboratory
  • 3Auburn University Depart of Health and Human Performance, Applied Exercise Physiology Laboratory
Further Information

Publication History

Publication Date:
28 October 2002 (online)

Also available at
    Permissions and Reprints

Abstract

The incidence of atherosclerosis and cardiovascular disease (CVD) in women increases following menopause and has been associated with a reduction in circulating estrogen. Increased CVD risk is also perpetuated by sedentary lifestyle. Growing evidence indicates that oxidation of lipoproteins leads to a powerful immune response, disruption of normal lipoprotein function, and deposition of atherosclerotic plaques. For example, once high-density lipoproteins (HDL) are oxidized, they lose the ability to a) participate in reverse transport of cholesterol to the liver, and b) protect low-density lipoproteins (LDL) against oxidation. The purpose of this study was to determine the effects of combining estrogen replacement and exercise upon lipid peroxidation of the HDL fraction (HDL-ox). Blood samples were drawn from 34 post-menopausal women from four groups: women who were not receiving estrogen replacement and who were sedentary (NSD) (n = 9); women who were not receiving estrogen replacement and who were participating in regular exercise (NEX) (n = 8); women who were receiving estrogen replacement and who were sedentary (ESD) (n = 8); and women who were receiving estrogen replacement and who were participating in regular exercise (EEX) (n = 9). Total-HDL cholesterol was significantly higher (p<0.05) in EEX when compared with NEX, NSD, and ESD. HDL-ox was assessed via malondialdehyde (MDA). Mean (± SEM) values for HDL MDA expressed in nM are as follows: NSD = 903.3 ± 118.4; NEX = 1226.7 ± 247.7; ESD = 876.7 ± 116.3; EEX = 537.4 ± 74.8. EEX lipid peroxidation was significantly (p = 0.02) lower than NEX. Lipid peroxidation tended to be lower in EEX than in NSD and ESD (p = 0.07). These data indicate that the combination of estrogen replacement and regular exercise in post-menopausal women may be most effective in reducing oxidation of HDL in vivo.

Key words

Atherosclerosis - cardiovascular disease - free radicals - high density lipoproteins - hormone replacement therapy

References

  • 1 Ayres S, Tang M, Subbiah M T. Estradiol-17ß as an antioxidant: some distinct features when compared with common fat-soluble antioxidants.  J Lab Clin Med . 1996;  128 367-375
    PubMedGoogle Scholar
  • 2 Beard CM, Barnard R J, Robbins D C, Ordovas J M, Schaefer EJ. Effects of diet and exercise on qualitative and quantitative measures of LDL and its susceptibility to oxidation.  Arterioscl Thromb Vasc Bio. 1996;  16 201-207
    PubMedGoogle Scholar
  • 3 Berliner J A, Naveb M, Fogelman A M, Frank J S, Demer L L, Edwardes P A, Watson A D, Lusis A J. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics.  Circulation. 1995;  91 2488-2496
    PubMedGoogle Scholar
  • 4 Bowling N, Matter W F, Gadski R A, McClure D B, Schreyer T, Dawson P A, lahos O J. LY295427, a novel hypocholesterolemic agent, enhances [3H]25-hydroxycholesterol binding to liver cytosolic proteins.  J Lipid Res. 1996;  37 2586-2598
    PubMedGoogle Scholar
  • 5 Bowry V W, Stanley K K, Stocker R. High density lipoprotein is the major carrier of hydroperoxides in human blood plasma from fasting donors.  Proc Natl Acad Sci. 1992;  89 10 316-10 320
    PubMedGoogle Scholar
  • 6 Bruckert E, Turpin G. Estrogens and progestins in post-menopausal women: influence on lipid parameters and cardiovascular risk.  Hormone Res. 1995;  43 100-103
    PubMedGoogle Scholar
  • 7 Brochier M L, Arwidson P. Coronary heart disease risk factors in women.  Eur Heart J. 1998;  19 A45-A52
    PubMedGoogle Scholar
  • 8 Christison J K, Rye K A, Stocker R. Exchange of oxidized cholesteryl linoleate between LDL and HDL by cholesterol ester transfer protein.  J Lipid Res. 1995;  36 2017-2026
    PubMedGoogle Scholar
  • 9 Criswell DS, Powers S, Dodd S, Lawler J, Edwards W, Renshler K, Grinton S. Cellular oxidative and antioxidant response in skeletal muscle to interval and continuous exercise training.  Med Sci Sports Exer. 1993;  25 1135-1140
    PubMedGoogle Scholar
  • 10 Devaraj S, Jialal T. Oxidized low-density lipoprotein and atherosclerosis.  Int J Clin Lab Res. 1996;  26 178-184
    PubMedGoogle Scholar
  • 11 de Waart F G, Moser U, Kok F J. Vitamin E supplementation in elderly lowers the oxidation rate of linoleic acid in LDL.  Atherosclerosis. 1997;  133 255-263
    CrossrefPubMedGoogle Scholar
  • 12 Egeland G M, Kuller K H, Matthews K A, Kelsey S F, Cauley J, Guzick D. Hormone replacement therapy and lipoprotein changes during early menopause.  Obstetr Gynecol. 1990;  76 776-782
    PubMedGoogle Scholar
  • 13 Folsom A R, Mink P J, Sellers T A, Hong C P, Zheng W, Potter J D. Hormonal replacement therapy and morbidity and mortality in a prospective study of postmenopausal women.  Am J Pub Health. 1995;  85 1128-1132
    PubMedGoogle Scholar
  • 14 Fruebis J, Ginzalez V, Silvestre M, Palinski W. Effect of probucol treatment on gene expression of VCAM-1, MCP-1, and M-CSF.  Arterioscl Thromb Vasc Biol. 1995;  17 1289-1302
    PubMedGoogle Scholar
  • 15 Gohil K, Viguie S, Stanley W C, Brooks G A, Packer L. Blood glutathione oxidation during human exercise.  J Appl Physiol. 1988;  64 115-119
    PubMedGoogle Scholar
  • 16 Goldstein J L, Ho Y K, Basu S K, Brown M S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein producing massive cholesterol deposition.  Proc Natl Acad Soc USA. 1979;  76 333-337
    PubMedGoogle Scholar
  • 17 Görög P. Activation of human blood monocytes by oxidized polyunsaturated fatty acids: a possible mechanism for generation of lipid peroxides in circulation.  Int J Exp Pathol. 1991;  72 227-237
    PubMedGoogle Scholar
  • 18 Gutteridge J MC, Quinlan G J. Malondialdehyde formation in the thiobarbituric acid test: the role of lipid radicals, iron salts, and metal chelators.  J Appl Biochem. 1983;  5 293-299
    PubMedGoogle Scholar
  • 19 Hahn M, Subbiah M T. Significant association of lipid peroxidation products with high density lipoproteins.  Biochem Mol Biol Internat. 1994;  33 699-704
    PubMedGoogle Scholar
  • 20 Heikkinen A M, Niskanen L, Yla-Herttuala S, Luoma J, Tuppruainen M T, Kamulainen M, Saarikoski S. Postmenopausal hormone replacement therapy and autoantibodies against oxidized LDL.  Maturitus. 1998;  29 155-161
    PubMedGoogle Scholar
  • 21 Ji L L, Stratman F W, Lardy H A. Enzymatic downregulation with exercise in rat skeletal muscle.  Arch Biochem Biophys. 1988;  263 137-149
    CrossrefPubMedGoogle Scholar
  • 22 Kanter M M, Hamlin R L, Unverferth D V, Davis H W, Merola A J. Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin.  J Appl Physiol. 1986;  59 1298-1303
    PubMedGoogle Scholar
  • 23 Kihlstöm M. Protection effect of endurance training against reoxygenation-induced injuries in the rat heart.  J Appl Physiol. 1990;  68 1672-1678
    PubMedGoogle Scholar
  • 24 Kwiterovich P G Jr. The antiatherogenic role of high density lipoprotein cholesterol.  Am J Cardiol. 1998;  82 13Q-21Q
    PubMedGoogle Scholar
  • 25 Lawler J M, Powers S K, Visser T, VanDijk H, Kordus M, Ji L L. Acute exercise and skeletal muscle antioxidant and metabolic enzymes: effects of fiber-type and age.  Am J Physiol. 1993;  265 R1344-R1350
    PubMedGoogle Scholar
  • 26 Mahfouz M M, Kawano H, Kummerow F A. Effect of cholesterol-rich diets with and without added vitamins E and C on the severity of atherosclerosis in rabbits.  Am J Clin Nutr. 1997;  66 1240-1249
    PubMedGoogle Scholar
  • 27 Martin A, Frei B. Both intracellular and extracellular Vitamin C inhibit atherogenic modification of LDL by human vascular endothelial cells.  Arterioscl Thromb Vasc Biol. 1997;  17 1583-1590
    PubMedGoogle Scholar
  • 28 McManus J, McEneny J, Thompson W, Young L S. The effect of hormone replacement therapy on the oxidation of low density lipoprotein in postmenopausal women.  Atherosclerosis. 1997;  135 73-81
    CrossrefPubMedGoogle Scholar
  • 29 McManus J, McEneny J, Young L S, Thompson W. The effect of various oestrogens and progestogens on the susceptibility of low density lipoproteins to oxidation in vitro.  Maturitus. 1996;  25 125-131
    PubMedGoogle Scholar
  • 30 Mehta J L, Chen L Y. Reversal of high-density lipoproteins of the effect of oxidized low-density lipoprotein on nitric oxide synthase protein expression in human platelets.  J Lab Clin Med. 1996;  127 287-295
    CrossrefPubMedGoogle Scholar
  • 31 Mena P, Maynar M, Gutierrez J M, Maynar J, Timon J, Campillo J E. Erythrocyte free radical scavenger enzymes in bicycle professional racers: adaptation to exercise.  Int J Sports Med. 1991;  12 563-566
    PubMedGoogle Scholar
  • 32 Morgan N A, Colling C L, Fye C L. Cardiovascular diseases in women: an equal opportunity killer.  J Am Pharmaceut Assoc. 1996;  36 360-369
    PubMedGoogle Scholar
  • 33 Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction.  Anal Biochem. 1979;  95 371-379
    CrossrefPubMedGoogle Scholar
  • 34 Ohmura H, Watanabe Y, Hatsumi C, Sato H, Daida H, Mokuno H, Yamaguchi H. Possible role of high susceptibility of high-density lipoprotein to lipid peroxidative modification and oxidized high-density lipoprotein in genesis of coronary artery spasm.  Atherosclerosis. 1999;  142 179-184
    CrossrefPubMedGoogle Scholar
  • 35 Palinski W, Yla-Herttuala S, Rosenfeld M E, Butler S W, Socher S A, Parthasarathy S, Curtiss L K, Witztum J L. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein.  Arteriosclerosis. 1990;  10 325-335
    PubMedGoogle Scholar
  • 36 Palmer H J, Paulson K E. Reactive oxygen species and antioxidants in signal transduction and gene expression.  Nutr Rev. 1997;  55 353-361
    PubMedGoogle Scholar
  • 37 Panasenko O M, Vol'nova TV, Azizova OA, Vladimirov Y A. Free radical modification of lipoproteins and cholesterol accumulation in cells upon atherosclerosis.  Free Rad Biol Med. 1991;  10 137-148
    CrossrefPubMedGoogle Scholar
  • 38 Pati N, Pati U. Paraoxonase gene polymorphism and coronary artery disease in Indian subjects.  Int J Cardiol. 1999;  66 165-168
    PubMedGoogle Scholar
  • 39 Powers S K, Criswell D, Lawler J M, Martin D, Lieu F K, Ji L L, Herb R. Rigorous exercise training increases superoxide dismutase activity in the ventricular myocardium.  Am J Physiol. 1993;  265 H2094-H2098
    PubMedGoogle Scholar
  • 40 Rifici V A, Khachadurian A K. Effects of dietary vitamin C and E supplementation on the copper mediated oxidation of HDL and on HDL mediated cholesterol efflux.  Atherosclerosis. 1996;  127 19-26
    CrossrefPubMedGoogle Scholar
  • 41 Robertson J D, Maughan R J, Duthie G G, Morrice P C. Increased blood antioxidant systems of runners in response to training load.  Clin Sci. 1991;  80 611-618
    PubMedGoogle Scholar
  • 42 Samsioe G. Cardioprotection by estrogens: mechanisms of action - the lipids.  Int J Fert Menopaus Stud. 1994;  39 43-49
    PubMedGoogle Scholar
  • 43 Sanchez-Quesada J L, Ortega H, Payes-Romero J, Serrat-Serrat J, Gonzalez-Sastre F, Lasuncion M A, Ordonez-Llanos J. LDL from aerobically-trained subjects shows higher resistance to oxidative modification than LDL from sedentary subjects.  Atherosclerosis. 1997;  132 207-213
    CrossrefPubMedGoogle Scholar
  • 44 Steinberg D. Arterial metabolism of lipoproteins in relation to atherogenesis.  Ann NY Acad Sci. 1990;  598 125-135
    PubMedGoogle Scholar
  • 45 Suc I, Escargueil-Blanc I, Troly M, Salvayre R, Negre-Salvayre A. HDL and ApoA prevent cell death of endothelial cells induced by oxidized LDL.  Arterioscl Thromb Vasc Biol. 1997;  17 2158-2166
    PubMedGoogle Scholar
  • 46 Taichakraichana N, Limpaphayom K, Ninlagarn T, Panyakhamlerd K, Chaikittisilpa S, Dusitsin N. A randomized trial of oral contraceptive and hormone replacement therapy on bone mineral density and coronary heart disease risk factors in postmenopausal women.  Obstetr Gynecol. 2000;  95 87-94
    PubMedGoogle Scholar
  • 47 Vasankari T J, Kujala U M, Vasankari T M, Ahotupa M. Reduced oxidized LDL levels after a 10-month exercise program.  Med Sci Sports Exer. 1998;  30 1496-1501
    PubMedGoogle Scholar
  • 48 Wakatsuki A, Ikenoue N, Sagara Y. Effects of estrogen on susceptibility to oxidation of low-density and high-density lipoprotein in postmenopausal women.  Maturitus. 1998;  28 229-234
    PubMedGoogle Scholar
  • 49 Wander R C, Du S H, Ketchum S D, Rowe K E. Effects of interaction of RRR-alpha-tocopherol acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy.  Am J Clin Nutr. 1996;  63 184-193
    PubMedGoogle Scholar
  • 50 Wells G, Herrington D M. The Heart and Estrogen/Progestin Replacement Study: what have we learned and what questions remain.  Drugs Aging. 1999;  15 419-422
    PubMedGoogle Scholar
  • 51 Wetzstein C J, Sherry-Brewer R A, Santanam N, Green N R, White-Welkley J E, Parthasarathy S. Does acute exercise affect the susceptibility of low density lipoprotein to oxidation?.  Free Rad Biol Med. 1998;  24 679-682
    CrossrefPubMedGoogle Scholar
  • 52 Wilmore J H, Costill D L. Physiology of Sport and Exercise. Champaign, IL; Human Kinetics 1999: 132-624
    Google Scholar

J. M. Lawler

Redox Biology & Cell Signaling Laboratory · Department of Health and Kinesiology · Texas A&M University

Rm 276B Read Bldg. · College Station · TX 77843-4243 · USA ·

Phone: (+1) 979 862 2038

Fax: (+1) 979 847 8987

Email: jml2621@neo.tamu.edu