Skip to main content
SpringerLink
Log in

Estrogen and the Vascular Injury Response

  • Conference paper
Biology of Menopause

Part of the book series: Serono Symposia USA ((SERONOSYMP))

  • 117 Accesses

Abstract

Gender plays an important role in the modulation of cardiovascular risk and events. Cardiovascular disease is less prevalent in premenopausal women than it is in age-matched men, but there is an increase in coronary risk and events in women after menopause (1). Although a prominent antiatherogenic response to estrogen is a reduction in plasma low density lipoprotein cholesterol (LDL-c) and an elevation of high density lipoprotein cholesterol (HDLc), other benefits are achieved by processes that are independent of changes in plasma lipid profiles (2–4). In this respect, estrogen therapy has proven to be effective in blunting the vascular injury response via both genomic and nongenomic mechanisms (5). Balloon injury of the rat carotid artery is an experimental paradigm that is commonly used to study mechanisms of atherogenesis. Estrogen minimizes the vascular injury response in this model through both direct antiproliferative effects and indirectly via the promotion of endothelial cell integrity and nitric oxide (NO) function (6–14). Additional protective effects of estrogen may be due to native antioxidant properties of the hormone (15). In this chapter, vasoprotective actions of estrogen exerted at the level of the arterial wall will be considered in the context of balloon injury models and hypercholesterolemia.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Sullivan JM, Fowlkes LP. The clinical aspects of estrogen and the cardiovascular system. Obstet Gynecol 1996;87:536–43.

    Article  Google Scholar 

  2. Wild RA. Estrogen: effects on the cardiovascular tree. Obstet Gynecol 1996;87:S2735.

    Article  Google Scholar 

  3. Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Card Dis 1995;38:199–210.

    Article  CAS  Google Scholar 

  4. Knopp RH, Zhu X, Bonet B. Effects of estrogens on lipoprotein metabolism and cardiovascular disease in women. Atherosclerosis 1994;110:S83–91.

    Article  Google Scholar 

  5. Farhat MY, Abi-Younes S, Ramwell PW. Non-genomic effects of estrogen and the vessel wall. Biochem Pharmacol 1996;51:571–76.

    Article  PubMed  CAS  Google Scholar 

  6. Chen SJ, Li H, Durand J, Oparil S, Chen YF. Estrogen reduces myointimal proliferation after balloon injury of rat carotid artery. Circulation 1996;93:577–84.

    Article  PubMed  CAS  Google Scholar 

  7. Foegh ML, Asotra S, Howell MH, Ramwell PW. Estradiol inhibition of arterial neointimal hyperplasia after balloon injury. J Vasc Surg 1994;19:722–26.

    Article  PubMed  CAS  Google Scholar 

  8. Rosselli M, Imthurn B, Keller PJ, Jackson EK, Dubey RK. Circulating nitric oxide (nitrate/nitrite) levels in postmenopausal women substituted with 17β-estradiol and norethisterone acetate. A two-year follow-up study. Hypertension 1995;25:84853.

    Article  Google Scholar 

  9. Keaney JF, Shwaery GT, Xu A, Nicolosi RJ, Loscalzo J, Foxall TL, Vita JA. 17βestradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation 1994;89:2251–59.

    Article  PubMed  CAS  Google Scholar 

  10. Herrington DM, Braden GA, Williams JK, Morgan TM. Endothelial-dependent coronary vasomotor responsiveness in postmenopausal women with and without estrogen replacement therapy. J Am Col Cardiol 1994;73:951–52.

    CAS  Google Scholar 

  11. Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, et al. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation 1994;89:52–60.

    Article  PubMed  CAS  Google Scholar 

  12. Nakano M, Sugioka K, Naito I, Takekoshi S, Niki E. Novel and potent biological antioxidants on membrane phospholipid peroxidation: 2-hydroxy estrone and 2hydroxy estradiol. Biochem Biophys Res Comm 1987;142:919–24.

    Article  PubMed  CAS  Google Scholar 

  13. Weiner CP, Knowles RG, Moncada S. Induction of nitric oxide synthases early in pregnancy. Am J Obstet Gynecol 1994;171:838–43.

    PubMed  CAS  Google Scholar 

  14. Weiner CP, Lizasoain I, Bayliss SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 1994;91:5212–16.

    Article  PubMed  CAS  Google Scholar 

  15. White CR, Darley-Usmar V, Oparil S. Gender and cardiovascular disease: recent insights. Trends Cardio Med 1997;7:94–100.

    Article  CAS  Google Scholar 

  16. White CR, Shelton J, Chen SJ, Durand J, Allen L, Darley-Usmar V, et al. Estrogen restores endothelial cell function in an experimental model of vascular injury. Circulation 1997;96:1624–30.

    Article  PubMed  CAS  Google Scholar 

  17. Stadius ML, Rowan R, Fleischhauer JF, Kernoff R, Billingham M, Gown AM. Time course and cellular characteristics of the iliac artery response to acute balloon injury. Arterio Thromb 1992;12:1267–73.

    Article  CAS  Google Scholar 

  18. Ferns GAA, Forster L, Stewart-Lee A, Konneh M, Nourooz-Zadeh J, Anggard EE. Probucol inhibits neointimal thickening and macrophage accumulation after balloon injury in the cholesterol-fed rabbit. Proc Natl Acad Sci USA 1992;89:1131216.

    Google Scholar 

  19. Wilcox JN, Scott NA. Potential role of the adventitia in arteritis and atherosclerosis. Int J Cardiol 1996;54(suppl 1):S21–35.

    Article  Google Scholar 

  20. Lynch CM, Hara PS, Leonard JC, Williams JK, Dean RH, Geary RL. Adeno-associated virus vectors for vascular gene delivery. Circ Res 1997;80:497–505.

    PubMed  CAS  Google Scholar 

  21. Shi Y, O’Brien JE, Fard A, Mannion JD, Wang D, Zalewski A. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation 1996;94:1655–64.

    Article  PubMed  CAS  Google Scholar 

  22. Shi Y, Pieniek M, Fard A, O’Brien J, Mannion JD, Zalewski A. Adventitial remodeling after coronary arterial injury. Circulation 1996;93:340–48.

    Article  PubMed  CAS  Google Scholar 

  23. Rao GN, Berk BC. Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. Circ Res 1992;70:593–99.

    Article  PubMed  CAS  Google Scholar 

  24. Sundaresan M, Yu Z-X, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H202 for platelet-derived growth factor signal transduction. Science 1995; 270:296–99.

    Article  PubMed  CAS  Google Scholar 

  25. Cooke JP, Tsao PS. Cytoprotective effects of nitric oxide. Circulation 1993;88:245154.

    Google Scholar 

  26. Oparil S, Levine RL, Chen SJ, Durand J, Chen YF. Sexually dimorphic response of the balloon injured rat carotid artery to hormone treatment. Circulation 1997; 95:1301–7.

    Article  PubMed  CAS  Google Scholar 

  27. Hanke H, Hanke S, Finking G, Muhic-Lohrer A, Muck AO, Schmahl FW, et al. Different effects of estrogen and progesterone on experimental atherosclerosis in female versus male rabbits. Quantification of cellular proliferation by bromodeoxyuridine. Circulation 1996;94:175–81.

    Article  PubMed  CAS  Google Scholar 

  28. Bhalla RC, Toth KF, Bhatty RA, Thompson LP, Sharma RV. Estrogen reduces proliferation and agonist-induced calcium increase in coronary artery smooth muscle cells. Am J Physiol 1997;272(4 Pt 2):H1996–2003.

    Google Scholar 

  29. Levine RL, Chen SJ, Durand J, Chen YF, Oparil S. Medroxyprogesterone attenuates estrogen-mediated inhibition of neointima formation after balloon injury of the rat carotid artery. Circulation 1996;94:2221–27.

    Article  PubMed  CAS  Google Scholar 

  30. Sacks FM, Gerhard M, Walsh BW. Sex hormones, lipoproteins, and vascular reactivity. Curr Opin Lipid 1995;6:161–66.

    Article  CAS  Google Scholar 

  31. Imthurn B, Rosselli M, Jaeger AW, Keller PJ, Dubey RK. Differential effects of hormone-replacement therapy on endogenous nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17 beta-estradiol valerate and cyproterone acetate or medroxyprogesterone acetate. J Clin Endocrinol Metab 1997;82: 388–94.

    Article  PubMed  CAS  Google Scholar 

  32. Adams MR, Register TC, Golden DL, Wagner JD, Williams JK. Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. Arterio Thromb Vasc Biol 1997;17:217–21.

    Article  CAS  Google Scholar 

  33. Yamada K, Hayashi T, Kuzuya M, Naito M, Asai K, Iguchi A. Physiological concentration of 17 beta-estradiol inhibits chemotaxis of human monocytes in response to monocyte chemotactic protein 1. Artery 1996;22:24–35.

    PubMed  CAS  Google Scholar 

  34. Frazier-Jessen MR, Kovacs EJ. Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages. J Immunol 1995; 154:1838--45.

    PubMed  CAS  Google Scholar 

  35. Caulin-Glaser T, Watson CA, Pardi R, Bender JR. Effects of 17beta-estradiol on cytokine-induced endothelial cell adhesion molecule expression. J Clin Invest 1996;98:36–42.

    Article  PubMed  CAS  Google Scholar 

  36. Chen YF, Oparil S. Effects of sex steroids in vascular injury. In: Endocrinology of cardiovascular function. Levin ER, ed. Norwell, MA: Kluwer Academic Publishers, 1998:45–59.

    Chapter  Google Scholar 

  37. Krasinski K, Spyridopoulos I, Asahara T, van der Zee R, Isner JM, Losordo DW. Estradiol accelerates functional endothelial recovery after arterial injury. Circulation 1997;95:1768–72.

    Article  PubMed  CAS  Google Scholar 

  38. Meurice T, Bauters C, Auffray JL, Vallet B, Hamon M, Valero F, et al. Basic fibroblast growth factor restores endothelium-dependent responses after balloon injury of rabbit arteries. Circulation 1996;93:18–22.

    Article  PubMed  CAS  Google Scholar 

  39. Asahara T, Bauters C, Pastore C, Kearney M, Rossow S, Bunting S, et al. Local delivery of vascular endothelial growth factor accelerates reendothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery. Circulation 1995;91:2793–801.

    Article  PubMed  CAS  Google Scholar 

  40. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801–9.

    Article  PubMed  CAS  Google Scholar 

  41. Cullinan-Bove K, Koos RD. Vascular endothelial growth factor/vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. Endocrinology 1993;133:829–37.

    Article  PubMed  CAS  Google Scholar 

  42. Charnock-Jones DS, Sharkey AM, Rajput-Williams J, Burch D, Schofield JP, Fountain SA, et al. Identification and localization of alternatively spliced mRNAs for vascular endothelial growth factor in human uterus and estrogen regulation in endometrial carcinoma cell lines. Biol Reprod 1993;48:1120–28.

    Article  PubMed  CAS  Google Scholar 

  43. Venema RC, Nishida K, Alexander RW, Harrison DG, Murphy TJ. Organization of the bovine gene encoding the endothelial nitric oxide synthase. Biochim Biophys Acta 1994;1218:413–20.

    Article  PubMed  CAS  Google Scholar 

  44. Guo JP, Panday MM, Consigny PM, Lefer AM. Mechanisms of vascular preservation by a novel NO donor following carotid artery intimal injury. Am J Physiol 1995;269:H1122–31.

    Google Scholar 

  45. Major TC, Overhiser RW, Panek RL. Evidence for NO involvement in regulating vascular reactivity in balloon-injured rat carotid artery. Am J Physiol 1995;269: H988–96.

    Google Scholar 

  46. Janssens S, Flaherty D, Nong Z, Varenne O, van Pelt N, Haustermans C, et al. Human endothelial nitric oxide synthase gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation after balloon injury in rats. Circulation 1998;97:1274–81.

    Article  PubMed  CAS  Google Scholar 

  47. Chen L, Daum G, Forough R, Clowes M, Walter U, Clowes AW. Overexpression of human endothelial nitric oxide synthase in rat vascular smooth muscle cells and in balloon-injured carotid artery. Circ Res 1998;82:862–70.

    Article  PubMed  CAS  Google Scholar 

  48. Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Am Coll Physicians 1994;121:936–41.

    CAS  Google Scholar 

  49. Gilligan DM, Badar DM, Panza JA, Quyyumi AA, Cannon RO. Effects of estrogen replacement therapy on peripheral vasomotor function in postmenopausal women. Am J Cardiol 1995;75:264–68.

    Article  PubMed  CAS  Google Scholar 

  50. De Caterina R, Libby P, Peng HB, Thannickal VJ, Rajavashisth TB, Gimbrone MA Jr, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995;96:60–68.

    Article  PubMed  Google Scholar 

  51. Shin WS, Hong YH, Peng HB, De Caterina R, Libby P, Liao JK. Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma. The role of constitutive NF-kappa B activity. J Biol Chem 1996;271:11317–24.

    Article  PubMed  CAS  Google Scholar 

  52. Peng HB, Libby P, Liao JK. Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B. J Biol Chem 1995;70:14214–19.

    Google Scholar 

  53. Lafont AM, Chai YC, Cornhill JF, Whitlow PL, Howe PH, Chisholm GM. Effect of alpha-tocopherol on restenosis after angioplasty in a model of experimental atherosclerosis. J Clin Invest 1995;95:1018–25.

    Article  PubMed  CAS  Google Scholar 

  54. Ruef J, Hu ZY, Yin L-Y, Wu Y, Hanson SR, Kelly AB, et al. Induction of vascular endothelial growth factor in balloon-injured baboon arteries: a novel role for reactive oxygen species in atherosclerosis. Circ Res 1997;81:24–33.

    Article  PubMed  CAS  Google Scholar 

  55. Arnal JF, Clamens S, Pechet C, Negre-Salvayre A, Allera C, Girolami JP, et al. Ethinylestradiol does not enhance the expression of NO synthase in bovine endothelial cells but increases the release of bioactive nitric oxide by inhibiting superoxide anion production. Proc Natl Acad Sci USA 1996;93:4108–13.

    Article  PubMed  CAS  Google Scholar 

  56. White CR, Brock TA, Chang LY, Crapo J, Briscoe P, Ku D, et al. Superoxide and peroxynitrite in atherosclerosis. Proc Natl Acad Sci USA 1994;91:1044–48.

    Article  PubMed  CAS  Google Scholar 

  57. White CR, Darley-Usmar V, McAdams M, Berrington WR, Gore J, Thompson JA, et al. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci USA 1996;93:8745–49.

    Article  PubMed  CAS  Google Scholar 

  58. Sugioka, K, Shimosegawa Y, Nakano M. Estrogens as natural antioxidants of membrane phospholipid peroxidation. FEBS Lett 1987;210:37–39.

    Article  PubMed  CAS  Google Scholar 

  59. Rifici VA, Khachadurian AK. The inhibition of low-density lipoprotein oxidation by 17β-estradiol. Metabolism 1992;41:1110–14.

    Article  PubMed  CAS  Google Scholar 

  60. Lacort M, Leal AM, Liza M, Martin C, Martinez R, Ruiz-Larrea MB. Protective effects of estrogens and catecholestrogens against peroxidative membrane damage in vitro. Lipids 1995;30:141–46.

    Article  PubMed  CAS  Google Scholar 

  61. Maziere C, Auclair M, Ronveaux MF, Salmon S, Santus R, Maziere JC. Estrogens inhibit copper and cell-mediated modification of low density lipoprotein. Atherosclerosis 1991;89:175–82.

    Article  PubMed  CAS  Google Scholar 

  62. Williams JK, Kim YD, Adams MR, Chen MF, Myers AK, Ramwell PW. Effects of estrogen on cardiovascular responses of premenopausal monkeys. J Pharmacol Exp Ther 1994;271:671–76.

    PubMed  CAS  Google Scholar 

  63. Giscaird V, Miller VM, Vanhoutte PM. Effect of 173-estradiol on endothelium-dependent responses in the rabbit. J Pharmacol Exp Ther 1988;244:19–22.

    Google Scholar 

  64. Hogg N, Struck A, Goss SP, Santanam N, Joseph J, Parthasarathy S, et al. Inhibition of macrophage-dependent low density lipoprotein oxidation by nitric-oxide donors. J Lipid Res 1995;36:1756–62.

    PubMed  CAS  Google Scholar 

  65. Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, et al. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 1994;269:26066–75.

    PubMed  CAS  Google Scholar 

  66. Struck AT, Hogg N, Thomas JP, Kalyanaraman B. Nitric oxide donor compounds inhibit the toxicity of oxidized low-density lipoprotein to endothelial cells. FEBS Lett 1995;361:291–94.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. C. Roger White
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suzanne Oparil
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Biology of Aging Program, National Institute on Aging, Gateway Building, Suite 2C231, 20892-9205, Bethesda, MD, USA

    Francis L. Bellino Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag New York, Inc.

About this paper

Cite this paper

White, C.R., Oparil, S. (2000). Estrogen and the Vascular Injury Response. In: Bellino, F.L. (eds) Biology of Menopause. Serono Symposia USA. Springer, New York, NY. https://doi.org/10.1007/978-0-387-21628-7_15

Download citation

  • DOI: https://doi.org/10.1007/978-0-387-21628-7_15

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4684-9530-0

  • Online ISBN: 978-0-387-21628-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation