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Lookup NU author(s): Professor Olaf Heidenreich
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OBJECTIVE: Cardiopulmonary bypass-mediated release of proinflammatory cytokines promotes the transendothelial migration of leukocytes. Among others, intercellular adhesion molecule (ICAM) is essential for this migratory process within the venous bypass graft, which finally contributes to a diminished early patency rate by thickening of the intima. Small interfering ribonucleic acids (siRNAs) are efficient and specific modulators of endogenous gene expression. This study describes the application of siRNAs to suppress ICAM-1 expression on the surface of human venous endothelial cells. METHODS: Primary cultures of human venous endothelial cells were either transfected with ICAM-1 siRNA, with a scrambled control siRNA or cultured without transfection. ICAM-1 expression was analyzed with or without TNF-alpha stimulation by flow cytometry. RESULTS: Upon TNF-alpha stimulation, cells transfected with ICAM-1 siRNA showed a six- to seven-fold decreased ICAM-1 expression compared to untransfected cells or cells transfected with the scrambled control siRNA. CONCLUSIONS: This is the first report that ICAM-1 expression can be effectively silenced by siRNAs on endothelial cells from human saphenous veins. This new technology may render novel therapeutic concepts to reduce early graft failure by protecting venous bypass grafts against early intra- or postoperative leukocyte infiltration.
Author(s): Walker T, Wendel HP, Tetzloff L, Heidenreich O, Ziemer G
Publication type: Article
Publication status: Published
Journal: European Journal of Cardio-Thoracic Surgery
Year: 2005
Volume: 28
Issue: 6
Pages: 816-820
Print publication date: 01/12/2005
ISSN (print): 1010-7940
ISSN (electronic): 1873-734X
URL: http://dx.doi.org/10.1016/j.ejcts.2005.09.009
DOI: 10.1016/j.ejcts.2005.09.009
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