Schreml, Stephan and Lehle, Karla and Birnbaum, Dietrich E. and Preuner, Juergen G. (2007) mTOR-inhibitors simultaneously inhibit proliferation and basal IL-6 synthesis of human coronary artery endothelial cells. INTERNATIONAL IMMUNOPHARMACOLOGY, 7 (6). pp. 781-790. ISSN 1567-5769,
Full text not available from this repository. (Request a copy)Abstract
Divergent results regarding the immunosuppressive effects of mammalian-target-of-rapamycin-(mTOR)-inhibitors on venous endothelial cells (ECs) have highlighted the importance of an accurate EC-model. The purpose of this study was to determine mTOR-inhibitor effects at a specific site of action - the human coronary-artery-ECs (HCAECs) - and to compare these data with results gained from cultures of human saphenous vein ECs (HSVECs). This EC-model could enable us to gain insight into site-specific pharmacodynamics and the immunosuppressive management of transplant vasculopathy. ECs were cultivated with rising concentrations of mTOR-inhibitors in the presence/absence of tumor necrosis factor (TNF). Cell counts, DNA-synthesis, cytotoxicity and concentrations of the cytokine IL-6 as well as the chemokines IL-8 and MCP-1 were measured. Half-maximal inhibitory effects on cell growth were reached after about 30 h incubation and both cell types showed equal responses regarding cell growth and DNA-synthesis after 48 h incubation time. mTOR-inhibitors failed to suppress basal/TNF-induced secretion of IL-8 and MCP-1, but IL-6 synthesis after TNF-induction was reduced to 35%. In contrast to human saphenous vein ECs (HSVECs), mTOR-inhibitors also reduced basal IL-6-secretion of HCAECs (to 55%) and cell proliferation was simultaneously inhibited within the same concentration range. Taking everything into account, we conclude that EC-proliferation is inhibited at concentrations needed to suppress TNF-stimulated IL-6 synthesis. Furthermore, the specific suppression of basal arterial IL-6-secretion and the delayed onset of the mTOR-inhibitor effect on HCAEC-proliferation (maximum reached after about 36 h) might be of relevance for the prevention of transplant vasculopathy at its initial stage, e.g. as a component of cardioplegic solutions. (C) 2007 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMOOTH-MUSCLE-CELLS; CARDIAC-TRANSPLANT RECIPIENTS; TUMOR-NECROSIS-FACTOR; ELUTING STENTS; SYSTEMIC VASCULITIS; PHARMACOLOGICAL-PROPERTIES; MYCOPHENOLATE-MOFETIL; NEOINTIMAL GROWTH; PROGENITOR CELLS; IN-VITRO; endothelial cells; coronary artery; cytokines; mTOR; proliferation; transplantation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Dec 2020 15:51 |
| Last Modified: | 08 Dec 2020 15:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32665 |
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