title: Human mesothelial cells express tissue factor when switched to proliferating state. Pharmacological modulation in vitro.
abstract: Covering the inner surface of small-diameter arterial prostheses with endothelial cells (ECs) has been proposed as a means of improving biocompatibility and thrombosis resistance. Because the availability of autologous ECs is limited, autologous human mesothelial cells (HMCs) have been suggested as a substitute for ECs. However, HMCs express tissue factor (TF) in vitro, a deleterious characteristic in vivo. We investigated the distribution of TF antigen and of its inhibitor, tissue factor pathway inhibitor, on HMCs and the effect of pharmacological agents on TF expression. TF antigen was measured by enzyme-linked immunosorbent assay and localized by confocal microscopy. Three distinct pools of TF antigen were demonstrated: within the cells, at the cell surface, and in the extracellular matrix. The effects of ilomedin (10 microg/ml) and heparin (500 U/ml), known to affect procoagulant activity, were evaluated by incubating HMCs for 24 h with or without these agents. Ilomedin, but not heparin, decreased TF antigen expression by 30% (P < 0.05). Despite the theoretical potential of HMCs as a vascular prosthesis lining, TF expression by HMCs remains a major drawback. A technique capable of blocking TF expression until the HMCs return to their resting state is needed. Genetic manipulation of HMCs may hold promise for such a technique.
authors.affiliation: Vascular and Thoracic Surgery Laboratory, Beaujon Teaching Hospital, Clichy, France. guy.leseche@bjn.ap-hop-paris.fr
authors.forename: J
authors.initials: J
authors.lastname: Ohan
authors.forename: G
authors.initials: G
authors.lastname: Lesèche
authors.forename: M A
authors.initials: MA
authors.lastname: Gilbert
authors.forename: G
authors.initials: G
authors.lastname: Trugnan
authors.forename: L
authors.initials: L
authors.lastname: Drouet
mesh_terms: D018929:Cell Culture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D008938:Mitosis / Q000502:physiology*; D009852:Omentum / Q000098:blood supply; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D010975:Platelet Aggregation Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin; D013925:Thromboplastin; D016285:Iloprost