title: Effects of cyclosporin A and dexamethasone on haemostatic and vasoactive functions of vascular endothelial cells.
abstract: Glucocorticoids reduce prostaglandin synthesis in cultured vascular endothelium, but their effects on other haemostatic functions are unclear. We examined the effects of dexamethasone and cyclosporin A (CSA) on cultured human umbilical vein endothelial cells (HUVEC). One, 10 and 50 micrograms/ml CSA and 1 microgram/ml dexamethasone (Dx) were added to the culture medium for 3 h, 3 days and 6 days and compared with HUVEC cultured in medium and serum alone. After assay of accumulated release of tissue type plasminogen activator (t-PA) and endothelin 1 (ET), cells were stimulated with 1 U/ml of human thrombin for 1 h and medium collected for RIA of 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thrombospondin (TSP), von Willebrand factor (vWf) and ELISA of plasminogen activator inhibitor 1 (PAI-1). CSA at 1 microgram/ml modestly reduced release of prostacyclin (PGI2) but had no reproducible effects on other metabolites. CSA at 10 and 50 micrograms/ml inhibited cell growth and thrombin stimulated release of PGI2 in a time- and dose-dependent manner. Inhibition of other endothelial metabolites was also observed at CSA 10 > micrograms/ml. Dexamethasone 1 microgram/ml reduced both cell number and PGI2 release and increased thrombin stimulated release of vWf, TSP and PAI-1 with increases in t-PA and endothelin 1 in the medium. CSA 1 microgram/ml and dexamethasone 1 microgram/ml together were additive in reducing PGI2 release and increasing PAI-1 secretion. These observations suggest a role for endothelial dysfunction in the hypertensive and thrombotic complications observed in steroid treated patients with CSA potentially contributing to such complications.
authors.affiliation: Department of Medicine, St George Hospital, NSW, Australia.
authors.forename: L Q
authors.initials: LQ
authors.lastname: Huang
authors.forename: J A
authors.initials: JA
authors.lastname: Whitworth
authors.forename: C N
authors.initials: CN
authors.lastname: Chesterman
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D019699:Thrombospondins; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014471:Umbilical Veins; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016232:Endothelins; D008562:Membrane Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D019699:Thrombospondins; D014841:von Willebrand Factor; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D016572:Cyclosporine; D011464:Epoprostenol; D013917:Thrombin; D010959:Tissue Plasminogen Activator