Östrogene und arterielle Gefäßwand

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.

Schlüsselwörter

Östrogen - Arteriosklerose - koronare Herzerkrankung

Keywords

Estrogen - atherosclerosis - coronary artery disease

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