PMID- 17572028
OWN - NLM
STAT- MEDLINE
DCOM- 20071221
LR  - 20151119
IS  - 0378-5122 (Print)
IS  - 0378-5122 (Linking)
VI  - 58
IP  - 1
DP  - 2007 Sep 20
TI  - In vitro effects of tibolone and its metabolites on human vascular coronary 
      cells.
PG  - 42-9
AB  - OBJECTIVES: Tibolone is a tissue selective compound with estrogenic, androgenic 
      and progestogenic properties in classical bioassays. It is used for alleviation 
      of menopausal symptoms and for osteoporosis prophylaxis in postmenopausal women. 
      Only few data are available regarding the effects of tibolone on the 
      cardiovascular system. We investigated therefore the in vitro effects of tibolone 
      and its metabolites on the vasculature under special controlled conditions, using 
      human female coronary endothelial and smooth muscle cells. METHODS: The effect on 
      the production of the following markers in endothelial cells from human female 
      coronary arteries was evaluated: nitric oxide synthase, prostacyclin, endothelin, 
      plasminogen-activator-inhibitor-1 (PAI-1), E-Selectin, Intercellular adhesion 
      molecule (ICAM-1), monocyte attracting protein-1 (MCP-1) and the precursor of 
      matrix metalloproteinase-1 (pro-MMP-1). Tibolone, its metabolites, estradiol 
      (E2), E2/norethisterone (NET) and E2/medroxyprogesterone acetate (MPA) were 
      tested at 0.1 microM and 1 microM. The markers were determined by enzyme 
      immunoassays in the cell supernatant. Cell proliferation of smooth muscle cells 
      from female coronary artery was measured by an adenosine triphosphate-assay. 
      RESULTS: Tibolone, its 3-hydroxy metabolites, E2/NET, E2/MPA and estradiol alone 
      had significant effects on the synthesis of all markers tested. The magnitude of 
      the tibolone effects, however, was mostly smaller than that of E2/NET and E2/MPA. 
      Concerning smooth muscle cells tibolone and its 3-hydroxy metabolites also 
      elicited an inhibition of the proliferation compared to control values. The 
      strongest effect here was found for E2/NET and E2 alone, whereas E2/MPA had no 
      effect. CONCLUSION: The results of this in vitro study conducted with cells of 
      the most important vascular bed with respect to the problem of cardiovascular 
      risk suggest that tibolone can positively influence the vasculature. However, 
      these tibolone effects may depend on intact vascular cells and may vary due to 
      the different atherosclerotic stages of the vessels. Thus, experimental studies 
      are useful to explore mechanisms, but clearly cannot replace clinical studies.
FAU - Seeger, H
AU  - Seeger H
AD  - Department of Endocrinology and Menopause, University's Women Hospital, 
      Calwerstrasse 7, 72 076 Tuebingen, Germany.
FAU - Kloosterboer, H J
AU  - Kloosterboer HJ
FAU - Studen, M
AU  - Studen M
FAU - Wallwiener, D
AU  - Wallwiener D
FAU - Mueck, A O
AU  - Mueck AO
LA  - eng
PT  - Journal Article
DEP - 20070615
PL  - Ireland
TA  - Maturitas
JT  - Maturitas
JID - 7807333
RN  - 0 (Biomarkers)
RN  - 0 (E-Selectin)
RN  - 0 (Endothelins)
RN  - 0 (Norpregnenes)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 4TI98Z838E (Estradiol)
RN  - C2QI4IOI2G (Medroxyprogesterone Acetate)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - FF9X0205V2 (tibolone)
RN  - T18F433X4S (Norethindrone)
SB  - IM
MH  - Biomarkers/*blood
MH  - Cells, Cultured
MH  - Coronary Vessels/*cytology/drug effects
MH  - E-Selectin/blood
MH  - Endothelins/blood
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epoprostenol/blood
MH  - Estradiol/pharmacology
MH  - Female
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Matrix Metalloproteinase 1/blood
MH  - Medroxyprogesterone Acetate/pharmacology
MH  - Muscle, Smooth, Vascular/cytology/*drug effects/metabolism
MH  - Nitric Oxide Synthase/blood
MH  - Norethindrone/pharmacology
MH  - Norpregnenes/*pharmacology
MH  - Plasminogen Activator Inhibitor 1/blood
MH  - Vascular Resistance/drug effects
EDAT- 2007/06/19 09:00
MHDA- 2007/12/22 09:00
CRDT- 2007/06/19 09:00
PHST- 2007/01/12 00:00 [received]
PHST- 2007/04/03 00:00 [revised]
PHST- 2007/04/29 00:00 [accepted]
PHST- 2007/06/19 09:00 [pubmed]
PHST- 2007/12/22 09:00 [medline]
PHST- 2007/06/19 09:00 [entrez]
AID - S0378-5122(07)00168-5 [pii]
AID - 10.1016/j.maturitas.2007.04.011 [doi]
PST - ppublish
SO  - Maturitas. 2007 Sep 20;58(1):42-9. doi: 10.1016/j.maturitas.2007.04.011. Epub 
      2007 Jun 15.