caa a22 4500 445822856 CHVBK 20180317145249.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s10616-010-9319-4 doi (NATIONALLICENCE)springer-10.1007/s10616-010-9319-4 Atorvastatin neutralises the thrombin-induced tissue factor expresion in endothelial cells via geranylgeranyl pyrophosphate [Elektronische Daten] [Vicenta Martínez-Sales, Virtudes Vila, Marcos Ferrando, Edelmiro Reganon] Statins may have beneficial effects in atherogenesis given their antithrombotic properties involving non-lipid mechanisms that modify endothelial function of tissue factor induction by thrombin. In this study, we investigate the effect of atorvastatin on tissue factor (TF) activity in thrombin-stimulated endothelial cells and its regulation through mevalonate or its derivatives. First subculture of human umbilical endothelial cells was used for this study. Cells were treated with thrombin and atorvastatin for different time intervals and dosage. Tissue factor activity was measured as Factor Xa generation induced by Tissue Factor-Factor VIIa complex on confluent cells. Our results show that atorvastatin prevents the thrombin-induced up-regulation of tissue factor activity in a concentration-dependent manner. Mevalonate and geranylgeranyl pyrophosphate reversed this inhibitory effect of atorvastatin on tissue factor activity, while the presence of farnesyl pyrophosphate did not prevent the atorvastatin effect on thrombin-induced tissue factor activity. Rho-kinase inhibitor did not affect the thrombin stimulation of tissue factor activity. High amount of hydrophobic isoprenoid groups decreases the thrombin-induced TF activity and may promote endothelial cell anti-thrombotic action. Rho kinase pathways do not have a major role in the thrombin-mediated TF activity. The inhibitory effect of atorvastatin on thrombin-induced TF activity was partially reversed by MVA and GGPP but not FPP. Springer Science+Business Media B.V., 2010 Atorvastatin nationallicence Tissue factor nationallicence Thrombin nationallicence Endothelial cells nationallicence Geranylgeranyl pyrophosphate nationallicence Martínez-Sales Vicenta Centro de Investigación, Hospital Universitario La Fe Avda, Campanar 21, 46009, Valencia, Spain aut Vila Virtudes Centro de Investigación, Hospital Universitario La Fe Avda, Campanar 21, 46009, Valencia, Spain aut Ferrando Marcos Departamento de Obstetricia y Ginecología, Hospital Universitario La Fe, Avda. Campanar 21, 46009, Valencia, Spain aut Reganon Edelmiro Centro de Investigación, Hospital Universitario La Fe Avda, Campanar 21, 46009, Valencia, Spain aut Cytotechnology Springer Netherlands 63/1(2011-01-01), 1-5 0920-9069 63:1<1 2011 63 10616 https://doi.org/10.1007/s10616-010-9319-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10616-010-9319-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Martínez-Sales Vicenta Centro de Investigación, Hospital Universitario La Fe Avda, Campanar 21, 46009, Valencia, Spain aut NATIONALLICENCE 700 1- Vila Virtudes Centro de Investigación, Hospital Universitario La Fe Avda, Campanar 21, 46009, Valencia, Spain aut NATIONALLICENCE 700 1- Ferrando Marcos Departamento de Obstetricia y Ginecología, Hospital Universitario La Fe, Avda. Campanar 21, 46009, Valencia, Spain aut NATIONALLICENCE 700 1- Reganon Edelmiro Centro de Investigación, Hospital Universitario La Fe Avda, Campanar 21, 46009, Valencia, Spain aut NATIONALLICENCE 773 0- Cytotechnology Springer Netherlands 63/1(2011-01-01), 1-5 0920-9069 63:1<1 2011 63 10616 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer