Hamostaseologie 2000; 20(04): 195-200
DOI: 10.1055/s-0037-1619495
Original article
Schattauer GmbH

Östrogene und arterielle Gefäßwand

Estrogens and the arterial vessel wall system
H. Hanke
1   Abteilung Innere Medizin II – Kardiologie der Universität Ulm, Ärztlicher Direktor: Prof. Dr. med. V. Hombach
› Author Affiliations
Further Information

Publication History

Publication Date:
22 December 2017 (online)

Zusammenfassung

In den vergangenen Jahren wurde eine Reihe verschiedener direkter Effekte von Östrogen an der arteriellen Gefäßwand selbst beschrieben (z.B. Hemmung der LDL-Cholesterin Akkumulation, antiproliferative Effekte auf glatte Muskelzellen). Außerdem konnte durch Östrogen auch eine endothelvermittelte, akut-vasodilatative Wirkung gezeigt werden. Die Tatsache, daß Progesteron in der Lage ist, den atheroprotektiven Effekt von Östrogen komplett zu hemmen, deutet möglicherweise auf einen direkten »interaktiven« Mechanismus beider Hormone an der arteriellen Gefäßwand hin. Diese experimentellen Daten können möglicherweise auch den negativen Ausgang der kürzlich publizierten HERS-Studie erklären, bei der postmenopausale Frauen mit gesicherter KHK eine kontinuierlich-kombinierte Gabe von equinem Östrogen mit Medroxyprogesteronazetat erhielten. Aufgrund neuerer Arbeiten wird u.a. eine mögliche Interaktion über gefäßwandständige Sexualhormonrezeptoren bei der atheroprotektiven Wirkungsvermittlung von Östrogen diskutiert. Die Aufklärung des exakten Wirkmechanismus von Östrogen kann langfristig eine alternative Therapie der Arteriosklerose unter Nutzung des »Östrogen-Wirkprinzips« ohne die eigentliche Geschlechtshormonwirkung ermöglichen.

Summary

Animal studies in different species have documented an inhibition of LDL-cholesterol accumulation in the arterial vessel wall by estrogen, as well as an directantiproliferative action on vascular smooth muscle cells. Progesterone is able to inhibit completely the atheroprotective action of estrogen, suggesting an interactive mechanism on the level of the arterial vessel wall. In this context, the importance of vascular estrogen receptors (subtypes ER-α and ER-α) in mediating the genomic processes are at the present discussed by several authors. Further research should focussed on the genomic pathways involved in the direct vascular estrogenic actions. The recent published HERS study has failed to show a beneficial effect of estrogen in postmenopausal women with confirmed coronary artery disease. However, these study is limited by the use of conjugated estrogens and a continuous-combined progesterone treatment. Therefore, additional experimental and clinical studies are needed to characterize different progestogens (i.e. norethisteron acetate, cyproterone acetate) in their interactive capacity with estrogen to avoid inhibitory effects on the protective estrogen action.

The exact detection of the mechanism(s) responsible for the vascular estrogen effect may probably allow to establish new approaches in the treatment of atherosclerosis related diseases.

 
  • Literatur:

  • 1 Adams MR, Register RC, Golden DL, Wagner JD, Williams JK. Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17: 217-21.
  • 2 Brehme U, Bruck B, Gugel N, Wehrmann M, Hanke S, Finking G, Haasis R, Schmahl FW, Hanke H. Aortic plaque size and endometrial proliferation in cholesterol-fed rabbits treated with estrogen plus continuous or sequential progesterone. Arteriocler Thromb Vasc Biol 1999; 19: 1930-7.
  • 3 Campos H, McNamara JR, Wilson PWF, Ordovas JM, Schaefer EJ. Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women. J Clin Endocrin 1988; 67: 30-5.
  • 4 Collins P, Rosano GMC, Sarrel PM, Ulrich L, Adamopoulos S, Beale CM, McNeill JG, Poole-Wilson PA. 17ß-estradiol attenuates acetylcholin-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation 1995; 92: 24-30.
  • 5 Croft P, Hannaford PC. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners Oral Contraception Study. Br J Med 1989; 298: 165-8.
  • 6 Fischer GM, Swain ML. Effects of estradiol and progesterone on the increased synthesis of collagen in atherosclerotic rabbit aortas. Atherosclerosis 185 (54) 177-85.
  • 7 Fröhlich M, Schunkert H, Hense H-W, Tropitzsch A, Hendricks P, Döring A, Riegger GAJ, Koenig W. Effects of hormone replacement therapies on fibrinogen and plasma viscosity in postmenopausal women. Brit J Haematol 1997; 100: 577-81.
  • 8 Haarbo J, Leth-Espensen P, Stender S, Christiansen C. Estrogen monotherapy and combined estrogen-progestogen replacement therapy attenuate aortic accumulation of cholesterol in ovariectomized cholesterol-fed rabbits. J Clin Invest 1991; 87: 1274-9.
  • 9 Hanke H, Hanke S, Bruck B, Brehme U, Gugel N, Finking G, Mück AO, Schmahl FW, Hombach V, Haasis R. Inhibition of the protective effect of estrogen by progesterone in experimental atherosclerosis. Atherosclerosis 1996; 121: 129-32.
  • 10 Hanke H, Hanke S, Finking G, Muhic-Lohrer A, Mück AO, Schmahl FW, Haasis R, Hombach V. Different effects of estrogen and progesterone on experimental atherosclerosis in female versus male rabbits. Circulation 1996; 94: 175-81.
  • 11 Hanke H, Kamenz J, Spieß J, Lenz C, Finking G, Hombach V. Effect of 17-Beta estradiol on pre-existing atherosclerotic lesions: Role of the endothelium. Atherosclerosis 1999; 147: 123-32.
  • 12 Henderson BE, Paganini-Hill A, Ross RK. Estrogen replacement therapy and protection from acute myocardial infarction. Am J Obstet Gynecol 1988; 159: 312-7.
  • 13 Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605-13.
  • 14 Karas RH, Hodgin JB, Kwoun M, Krege JH, Aronovitz M, Mackey W, Gustafsson JA, Korach KS, Smithies O, Mendelsohn ME. Estrogen inhibits the vascular injury response in estrogen receptor ß-deficient female mice. Proc Natl Acad Sci 1999; 96: 15133-6.
  • 15 Kuhl H. Hormonale Kontrazeption und Substitutionstherapie. Die Bedeutung des Gestagens für kardiovasculäre Erkrankungen. Geburtsh Frauenheilk 1992; 52: 653-62.
  • 16 Kuiper GGJM, Enmark E, Pelto-Huikko Nilsson S, Gustafsson JA. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci 1996; 93: 5925-30.
  • 17 Lafferty FW, Fiske ME. Postmenopausal estrogen replacement. A long-term cohort study. Am J Med 1994; 97: 66-77.
  • 18 Lindberg UB, Crona N, Stigendahl L, Teger-Nilsson AC, Silferstolpe G. A comparison between effects of estradiol valerate and low dose ethinyl estradiolon haemostasis parameters. Thrombos Haemostas 1989; 61: 65-9.
  • 19 Ludden JB, Bruger M, Wright IS. Experimental atherosclerosis. IV. Effect of testosterone propionate and estradiol dipropionate on experimental atherosclerosis in rabbits. Arch Path 1942; 33: 58-62.
  • 20 Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. NEJM 1999; 340: 1801-11.
  • 21 Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK, Szklo M. Association of hormone replacement therapy with various cardiovascular risk factors in postmenopausal women. N Engl J Med 1993; 328: 1069-75.
  • 22 Oparil S, Levine RL, Chen S-J, Durand J, Chen YF. Sexually dimorphic response of the ballon-injured rat carotid artery to hormone treatment. Circulation 1997; 95: 1301-7.
  • 23 Paganini-Hill A, Ross RK, Henderson BE. Postmenopausal oestrogen treatment and stroke: a prospective study. Br Med J 1988; 297: 519-22.
  • 24 Persson I, Adami H-O, Bergkvist L, Lindgren A, Pettersson B, Hoover R, Schairer C. Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: Results of a prospective study. Brit Med J 1989; 298: 147-51.
  • 25 Reiss SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, Brinker JA. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation 1994; 89: 52-60.
  • 26 Rosano GMC, Sarrel PM, Poole-Wilson PA, Collins P. Beneficial effect of oestrogen on exercis-induced myocardial ischaemia in women with coronary artery disease. Lancet 1993; 342: 133-6.
  • 27 Salomaa V, Rasi V, Pekkanen J, Vahtera E, Jauhiainen M, Vartiainen E, Ehnhoilm C, Tuomilehto J, Myllyla G. Association of hormone replacement therapy with haemostatic and other cardiovascular risk factors: the FINRISK Haemostasis Study. Arterioscler Thromb Vasc Biol 1995; 15: 1549-55.
  • 28 Sattar N, Greer IA, Rumley A, Steward G, Shepherd J, Packard CJ, Lowe GD. A longitudinal study of the relationships between haemostatic, lipid, and oestradiol changes during normal human pregnancy. Thromb Haemost 1999; 81: 71-5.
  • 29 Shi-Juan C, Huaibin L, Durand J, Oparil S, Yui-Fai C. Estrogen reduces myointimal proliferation after balloon injury of rat carotid artery. Circulation 1996; 93: 577-84.
  • 30 Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the Nurses’ Health Study. N Engl J Med 1991; 325: 756-62.
  • 31 Steinberg KK, Thacker SB, Smith SJ, Stroup DF, Zack MM, Flanders WD, Berkelman RL. A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. JAMA 1991; 265: 1985-90.
  • 32 Stiller S, Hanke S, Finking G, Spieß J, Lenz C, Hombach V, Hanke H. Effekt von Cyproteronacetat und Norethisteronenantat in Kombination mit Östrogen an einem experimentellen Atherosklerosemodell (Abstrakt). Perfusion 1999; 12: 99.
  • 33 The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1995; 273: 199-208.
  • 34 Wagner JD, Clarkson TB, St Clair RW, Schwenke DC, Shively CA, Adams MR. Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal Cynomolgus monkeys. J Clin Invest 1991; 88: 1995-2002.
  • 35 Williams JK, Honore EK, Washburn SA, Clarkson TB. Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys. J Am Coll Cardiol 1994; 24: 1757-61.
  • 36 Vargas R, Wroblewska B, Rego A, Hatch J, Ramwell PW. Oestradiol inhibits smooth muscle cell proliferation of pig coronary artery. Brit J Pharm 1993; 109: 612-7.