Document Detail


Inhibition of adhesion molecule expression on human venous endothelial cells by non-viral siRNA transfection.
MedLine Citation:
PMID:  17367508     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Expression of adhesion molecule receptors on venous endothelial cells crucially influences the fate of venous grafts by mediating leukocyte-endothelium interactions. These interactions include adhesion of leukocytes to the endothelium, followed by transendothelial migration, leading to neointimal hyperplasia (NIH) and finally graft occlusion. Therefore, inhibition of adhesion molecule expression may be a promising strategy to improve the quality of venous grafts. We tested the efficiency of non-viral transfection of human venous endothelial cells (HVEC) with short interfering RNA (siRNA) to specifically down-regulate adhesion molecule expression. METHODS: Primary cultures of HVEC were examined for expression of the adhesion molecules ICAM1, VCAM1 and E-selectin (SELE) after non viral siRNA transfection. Adhesion molecule expression was measured by flow cytometry, real-time polymerase chain reaction and immunoblotting after stimulation with TNF-alpha, an inflammatory cytokine. RESULTS: Non-transfected cells showed a strong increase of adhesion molecule expression following cytokine stimulation (P < 0.01). Upon transfection with specific siRNAs a sixfold decrease in ICAM1 (P < 0.001) and SELE expression and cell positivity (P < 0.05) and a twofold decrease in VCAM1 expression and cell positivity (P < 0.01) P could be observed. SiRNA-mediated gene suppression of adhesion molecules was also reflected by corresponding decreases in adhesion protein and transcript levels. CONCLUSIONS: The expression of adhesion molecules on HVECs can be effectively inhibited by specific siRNAs using a safe, non-viral transfection approach. This is a promising tool to pre-condition venous bypass grafts in order to interfere with endothelium-leukocyte interactions and to prohibit neointima thickening or atherosclerosis, which are regarded to be the most important causes of venous graft failure.
Authors:
Tobias Walker; Hans P Wendel; Liane Tetzloff; Claudia Raabe; Olaf Heidenreich; Perikles Simon; Albertus M Scheule; Gerhard Ziemer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  11     ISSN:  1582-1838     ISO Abbreviation:  J. Cell. Mol. Med.     Publication Date:    2007 Jan-Feb
Date Detail:
Created Date:  2007-03-19     Completed Date:  2007-05-04     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  Romania    
Other Details:
Languages:  eng     Pagination:  139-47     Citation Subset:  IM    
Affiliation:
Department of Thoracic, Cardiac and Vascular Surgery, Tuebingen University Hospital, Tuebingen, Germany. tobias.walker@med.uni-tuebingen.de
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MeSH Terms
Descriptor/Qualifier:
Cell Adhesion Molecules / antagonists & inhibitors*
Cells, Cultured
Endothelial Cells / drug effects*,  metabolism
Endothelium, Vascular / cytology,  metabolism
Fluorescein-5-isothiocyanate
Fluorescent Dyes
Humans
Intercellular Adhesion Molecule-1 / pharmacology*
RNA, Small Interfering / genetics*
Saphenous Vein / cytology,  metabolism
Transfection
Tumor Necrosis Factor-alpha / pharmacology
Veins / cytology*,  metabolism
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Fluorescent Dyes; 0/RNA, Small Interfering; 0/Tumor Necrosis Factor-alpha; 126547-89-5/Intercellular Adhesion Molecule-1; 3326-32-7/Fluorescein-5-isothiocyanate

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