[Effect of tibolone on vascular markers of human female coronary arteries - comparison with estradiol/norethisterone].
OBJECTIVE
Tibolone, a synthetic norethynodrel derivative, is effective at alleviating climacteric complaints and for osteoporosis prophylaxis. Concerning the cardiovascular system little data are available on possible direct effects on the vasculature compared with hormone replacement therapy. Since tibolone is pharmacologically best comparable to an estradiol/norethisterone combination (E2/NET), the aim of the present study was to compare these treatment regimens with respect to their effects on human vascular cells, this being the first study to investigate this question. -


METHODS
Human female coronary arteries were used, the most appropriate vessels for our issue in question. The experiments were conducted with endothelial cells as well as smooth muscle cells. Tibolone and E2/NET were tested at the concentrations 0.1, 1 und 10 microM. Incubation time was 24 h for endothelial cell cultures and 7 days for smooth muscle cell cultures. The effects on markers of pathophysiologically different problems were studied in a comparable manner: Markers of endothelial function such as prostacyclin, endothelin and plasminogen-activator-inhibitor-1 (PAI-1), markers of plaque initiation such as the adhesion molecules E-Selectin, ICAM-1 and the monocyte attraction protein-1 (MCP-1) and markers of plaque stability such as the precursor of the matrix-metalloproteinase-1 (pro-MMP-1). -


RESULTS
Tibolone reduced the synthesis of endothelin as well as the concentrations of E-Selectin, PAI-1 and pro-MMP-1. The magnitude of the effects on these markers varied and was in the range of 11-42 %. similar inhibitions were seen for E2/NET; yet a significantly stronger inhibitory effect was found for pro-MMP-1. Moreover, E2/NET also reduced concentrations of ICAM-1 and MCP-1. Concerning smooth muscle cells only E2/NET was able to elicit an anti-proliferative effect. -


CONCLUSIONS
Tibolone can positively influence the synthesis of markers in cell cultures of human female coronary artery which modulate vascular tone and which play a decisive role in the various stages of atherosclerosis. In this respect estradiol combined with norethisterone is as potent as tibolone, in addition this combination is partially more effective and able to influence a wider range of markers which are important in the early stages of atherogenesis or for the stability of atherosclerotic plaques. Experimental studies such as the present one are useful to explore mechanisms, but clearly cannot replace clinical studies.
Mueck
A O
AO
Bereich Endokrinologie und Menopause, Universitäts-Frauenklinik, Tübingen. endo.meno@med.uni-tuebingen.de
Seeger
H
H
Wallwiener
D
D
D002455:Cell Division / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009640:Norethindrone / Q000494:pharmacology*; D009652:Norpregnenes / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D009652:Norpregnenes; D004958:Estradiol; C027385:tibolone; D009640:Norethindrone