Der Einfluss der Sexualhormone auf die Gefäßbiologie der Venen^[*]

Zusammenfassung

Die wichtigsten Erkrankungen der Venen stellen Varikose, Thrombose und Phlebosklerose, in diesem Artikel als chronisch-venöse Erkrankung (CVE) bezeichnet, dar. Es ist unklar, wie Varikose entsteht. Die Forschung der letzten Jahre hat gezeigt, dass Gefäßerkrankungen die Folge von Gefäßwandumbauvorgängen darstellen. Diese werden von molekularen Mechanismen gesteuert. Da das Auftreten von Varikose klinisch mit Schwangerschaft und Hormonapplikation koinzidiert, beschäftigt sich der folgende Artikel mit den Wirkungen von Sexualhormonen auf bekannte Proteine, die das Gefäßremodeling steuern. Derzeit sind die Schlüsselmechanismen des vaskulären Remodelings der Venen noch nicht ausreichend erforscht, um eine direkte Umsetzung in die praktische Medizin zu rechtfertigen.

Summary

Varicosis, thrombosis and phlebosclerosis represent the spectrum of chronic venous disease. The mechanisms underlying varicosis are unknown. Recent data suggest that vascular disease results from transmural remodeling processes, that are triggered by molecular events. Because varicosis is clinically related to pregnancy and hormone treatment, this manuscript deals with the effects of sex steroids on proteins that are controlling vascular remodeling. Key mechanisms of vascular remodeling of veins are not sufficiently known to justify therapeutic recommendations.

Résumé

Les plus importantes pathologies veineuses sont la varicose, les thromboses et la sclerose des veines, ainsi les maladies veineuses chroniques. Le developpement de la varicose n’est pas éclairé. Les études sciéntifiques recentes ont montrées que les maladies veineuses sont les sequelles du remodeling des vaisseaux. Lequel est dirigé par des mechanismes moleculaires. Car l’ incidence des varicoses est lié avec la grossesse et l’application des hormones, cet article trait l’effet des hormones sur divers proteines, qui réglementent le fonctionnement des vaisseaux. Les points cléfs du fonctionnement du remodeling des vaissaux ne sont pas encore assez étudiés, qu’on puisse présenter des recommendations thérapeutiques par traitement hormonel.

La biologie veineuse sous l’influence des hormones

Schlüsselwörter

Östrogen - Progesteron - chronisch-venöse Insuffizienz

Keywords

Estrogen - progesterone - chronic venous insufficiency

Mots clés

Oestrogènes - gestagènes - insuffisance veineuse chronique

^* Diese Arbeit wurde vom Medizinisch- Wissenschaftlichen Fonds des Bürgermeisters der Bundeshauptstadt Wien, rojektnummer 1775, unterstützt

• Literatur

• 1 Abramson JH, Hopp C, Epstein LM. The epidemiology of varicose veins. A survey in western Jerusalem. J Epidemiol Community Health 1981; 35: 213-7.
• 2 Badier-Commander C, Verbeuren T, Lebard C, Michel JB, Jacob MP. Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation. J Pathol 2000; 192: 105-12.
• 3 Balbin M, Fueyo A, Knauper V, Pendas AM, Lopez JM, Jimenez MG. et al. Collagenase 2 (MMP-8) expression in murine tissue-remodeling processes. Analysis of its potential role in postpartum involution of the uterus. J Biol Chem 1998; 273: 23959-68.
• 4 Bilsel AS, Moini H, Tetik E, Aksungar F, Kaynak B, Ozer A. 17Beta-estradiol modulates endothelin-1 expression and release in human endothelial cells. Cardiovasc Res 2000; 46: 579-84.
• 5 Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000; 1477: 267-83.
• 6 Callam MJ. Epidemiology of varicose veins. Br J Surg 1994; 81: 167-73.
• 7 Castelli WP. Epidemiology of coronary heart disease: the Framingham study. Am J Med 1984; 76: 4-12.
• 8 Celentano DC, Frishman WH. Matrix metalloproteinases and coronary artery disease: a novel therapeutic target. J Clin Pharmacol 1997; 37: 991-1000.
• 9 Colburn P, Buonassisi V. Estrogen-binding sites in endothelial cell cultures. Science 1978; 201: 817-9.
• 10 Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987; 316: 1105-10.
• 11 Conrad KP, Joffe GM, Kruszyna H, Kruszyna R, Rochelle LG, Smith RP. et al. Identification of increased nitric oxide biosynthesis during pregnancy in rats. Faseb J 1993; 7: 566-71.
• 12 Cooke JP, Tsao PS. Cytoprotective effects of nitric oxide. Circulation 1993; 88: 2451-4.
• 13 Dai-Do D, Espinosa E, Liu G, Rabelink TJ, Julmy F, Yang Z. et al. 17 beta-estradiol inhibits proliferation and migration of human vascular smooth muscle cells: similar effects in cells from postmenopausal females and in males. Cardiovasc Res 1996; 32: 980-5.
• 14 Enmark E, Gustafsson JA. Oestrogen receptors – an overview. J Intern Med 1999; 246: 133-8.
• 15 Forstermann U, Pollock JS, Schmidt HH, Heller M, Murad F. Calmodulin-dependent endothelium- derived relaxing factor/nitric oxide synthase activity is present in the particulate and cytosolic fractions of bovine aortic endothelial cells. Proc Natl Acad Sci USA 1991; 88 (Suppl. 05) 1788-92.
• 16 Gandhi RH, Irizarry E, Nackman GB, Halpern VJ, Mulcare RJ, Tilson MD. Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins. J Vasc Surg 1993; 18: 814-20.
• 17 Gao J, Tseng L. Progesterone receptor (PR) inhibits expression of insulin-like growth factor-binding protein-1 (IGFBP-1) in human endometrial cell line HEC-1B: characterization of the inhibitory effect of PR on the distal promoter region of the IGFBP-1 gene. Mol Endocrinol 1997; 11: 973-9.
• 18 Garcia-Cardena G, Fan R, Shah V, Sorrentino R, Cirino G, Papapetropoulos A. et al. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998; 392: 821-4.
• 19 Giangrande PH, McDonnell DP. The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene. Recent Prog Horm Res 1999; 54: 291-313.
• 20 Hamilton CA, Berg G, McIntyre M, McPhaden AR, Reid JL, Dominiczak AF. Effects of nitric oxide and superoxide on relaxation in human artery and vein. Atherosclerosis 1997; 133: 77-86.
• 21 Harder DR, Coulson PB. Estrogen receptors and effects of estrogen on membrane electrical properties of coronary vascular smooth muscle. J Cell Physiol 1979; 100: 375-82.
• 22 Hayashi T, Fukuto JM, Ignarro LJ, Chaudhuri G. Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits: implications for atherosclerosis. Proc Natl Acad Sci USA 1992; 89: 11259-63.
• 23 Herkert O, Kuhl H, Busse R, Schini-Kerth VB. The progestin levonorgestrel induces endothelium- independent relaxation of rabbit jugular vein via inhibition of calcium entry and protein kinase C: role of cyclic AMP. Br J Pharmacol 2000; 130: 1911-8.
• 24 Hodges YK, Tung L, Yan XD, Graham JD, Horwitz KB, Horwitz LD. Estrogen receptors alpha and beta: prevalence of estrogen receptor beta mRNA in human vascular smooth muscle and transcriptional effects. Circulation 2000; 101: 1792-8.
• 25 Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S. et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997; 138: 863-70.
• 26 Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996; 93: 5925-30.
• 27 Lind L, Hall J, Larsson A, Annuk M, Fellstrom B, Lithell H. Evaluation of endothelium-dependent vasodilation in the human peripheral circulation. Clin Physiol 2000; 20: 440-8.
• 28 Losordo DW, Kearney M, Kim EA, Jekanowski J, Isner JM. Variable expression of the estrogen receptor in normal and atherosclerotic coronary arteries of premenopausal women. Circulation 1994; 89: 1501-10.
• 29 Lüscher TF, Barton M. Biology of the endothelium. Clin Cardiol. 1997 20 (Suppl 2): II-3-10.
• 30 Maffei FH, Magaldi C, Pinho SZ, Lastoria S, Pinho W, Yoshida WB. et al. Varicose veins and chronic venous insufficiency in Brazil: prevalence among 1755 inhabitants of a country town. Int J Epidemiol 1986; 15: 210-7.
• 31 Makela S, Savolainen H, Aavik E, Myllarniemi M, Strauss L, Taskinen E. et al. Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta. Proc Natl Acad Sci USA 1999; 96: 7077-82.
• 32 Marbaix E, Kokorine I, Donnez J, Eeckhout Y, Courtoy PJ. Regulation and restricted expression of interstitial collagenase suggest a pivotal role in the initiation of menstruation. Hum Reprod 1996; 11 (Suppl. 02) 134-43.
• 33 Mendelsohn ME, Karas RH. Estrogen and the blood vessel wall. Curr Opin Cardiol 1994; 9: 619-26.
• 34 Mercuro G, Pitzalis L, Podda A, Zoncu S, Pilia I, Melis GB. et al. Effects of acute administration of natural progesterone on peripheral vascular responsiveness in healthy postmenopausal women. Am J Cardiol 1999; 84: 214-8.
• 35 Morey AK, Pedram A, Razandi M, Prins BA, Hu RM, Biesiada E. et al. Estrogen and progesterone inhibit vascular smooth muscle proliferation. Endocrinology 1997; 138: 3330-9.
• 36 Murphy G, Knauper V, Cowell S, Hembry R, Stanton H, Butler G. et al. Evaluation of some newer matrix metalloproteinases. Ann NY Acad Sci 1999; 878: 25-39.
• 37 Murphy G, Stanton H, Cowell S, Butler G, Knauper V, Atkinson S. et al. Mechanisms for pro matrix metalloproteinase activation. Apmis 1999; 107: 38-44.
• 38 Nickenig G, Strehlow K, Wassmann S, Baumer AT, Albory K, Sauer H. et al. Differential effects of estrogen and progesterone on AT(1) receptor gene expression in vascular smooth muscle cells. Circulation 2000; 102: 1828-33.
• 39 Pace P, Taylor J, Suntharalingam S, Coombes RC, Ali S. Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha. J Biol Chem 1997; 272: 25832-8.
• 40 Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524-6.
• 41 Parra JR, Cambria RA, Hower CD, Dassow MS, Freischlag JA, Seabrook GR. et al. Tissue inhibitor of metalloproteinase-1 is increased in the saphenofemoral junction of patients with varices in the leg. J Vasc Surg 1998; 28: 669-75.
• 42 Perrot-Applanat M, Cohen-Solal K, Milgrom E, Finet M. Progesterone receptor expression in human saphenous veins. Circulation 1995; 92: 2975-83.
• 43 Perrot-Applanat M, Groyer-Picard MT, Garcia E, Lorenzo F, Milgrom E. Immunocytochemical demonstration of estrogen and progesterone receptors in muscle cells of uterine arteries in rabbits and humans. Endocrinology 1988; 123: 1511-9.
• 44 Rorie DK, Muldoon SM. Increased reactivity of isolated rabbit saphenous vein after treatment with estrogen and progesterone. Blood Vessels 1979; 16: 252-8.
• 45 Shimonovitz S, Hurwitz A, Hochner-Celnikier D, Dushnik M, Anteby E, Yagel S. Expression of gelatinase B by trophoblast cells: downregulation by progesterone. Am J Obstet Gynecol 1998; 178: 457-61.
• 46 Silva de Sa MF, Meirelles RS. Vasodilating effect of estrogen on the human umbilical artery. Gynecol Invest 1977; 8: 307-13.
• 47 Skudder Jr PA, Farrington DT, Weld E, Putman C. Venous dysfunction of late pregnancy persists after delivery. J Cardiovasc Surg (Torino) 1990; 31: 748-52.
• 48 Sparey C, Sissons G, Haddad N, Rosser S, de Cossart L. Serial colour flow duplex scanning of the veins of the lower limb throughout pregnancy. Br J Obstet Gynaecol 1999; 106: 557-62.
• 49 Thompson RW, Parks WC. Role of matrix metalloproteinases in abdominal aortic aneurysms. Ann N Y Acad Sci 1996; 800: 157-74.
• 50 Touitou I, Cavailles V, Garcia M, Defrenne A, Rochefort H. Differential regulation of cathepsin D by sex steroids in mammary cancer and uterine cells. Mol Cell Endocrinol 1989; 66: 231-8.
• 51 Ueland K, Parer JT. Effects of estrogens on the cardiovascular system of the ewe. Am J Obstet Gynecol 1966; 96: 400-6.
• 52 Van Buren GA, Yang DS, Clark KE. Estrogeninduced uterine vasodilatation is antagonized by L-nitroarginine methyl ester, an inhibitor of nitric oxide synthesis. Am J Obstet Gynecol 1992; 167: 828-33.
• 53 Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Schmidt K. et al. Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP. J Biol Chem 1993; 268: 1842-6.
• 54 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.
• 55 Wingrove CS, Garr E, Godsland IF, Stevenson JC. 17beta-oestradiol enhances release of matrix metalloproteinase-2 from human vascular smooth muscle cells. Biochim Biophys Acta 1998; 1406: 169-74.