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Eur J Cardiothorac Surg 2005;28:816-820
© 2005 Elsevier Science NL

Suppression of ICAM-1 in human venous endothelial cells by small interfering RNAs

^a Department of Thoracic, Cardiac and Vascular Surgery, Tuebingen University Hospital, Hoppe-Seyler-Straße 3, 72076 Tuebingen, Germany
^b Department of Molecular Biology, Tuebingen University, Auf der Morgenstelle 5, 72076 Tuebingen, Germany

Received 1 April 2005; received in revised form 12 September 2005; accepted 15 September 2005.

^_* Corresponding author. Tel.: +49 7071 2986611; fax: +49 7071 293298. (Email: tobias.walker{at}med.uni-tuebingen.de).

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- stimulation by flow cytometry. Results: Upon TNF- 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.

Key Words: CABG • Venous grafts • Endothelium • Gene therapy

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