Document Detail

Adenoviral delivery of a constitutively active retinoblastoma mutant inhibits neointima formation in a human explant model for vein graft disease.
MedLine Citation:
PMID:  14567067     Owner:  NLM     Status:  MEDLINE    
Intimal hyperplasia resulting from vascular injury remains a major obstacle in the long-term success of coronary artery bypass grafts. Inhibition of smooth muscle cell (SMC) proliferation using adenoviral gene transfer of cell cycle inhibitors resulted in reduced neointima formation in various animal models. However, little is known about the effect on human SMCs and neointima formation. Here we report the effects of infection with an adenoviral vector encoding a constitutively active form of the retinoblastoma gene (Ad. delta Rb) on proliferation of human saphenous vein SMCs (HSVSMCs) and neointima formation in organ cultures of human saphenous vein. Proliferation of SMCs was inhibited dose-dependently after infection with Ad. delta Rb. A near-total inhibition was found at an Ad. delta Rb concentration of 10(8) pfu/ml. Organ cultures of human saphenous vein segments were used to evaluate the effect of Ad. delta Rb infection on neointima formation and vein graft disease. Segments cultured for 4 weeks develop a neointima that is morphologically highly similar to early initimal lesions found in pathological vein grafts in vivo. Infection of saphenous vein segments with 2 x 10(9) pfu/ml Ad. delta Rb resulted in a 59% reduction of neointimal area when compared to uninfected counterparts, whereas infection with control adenovirus, Ad.LacZ, had no significant effect. The results of this study show that Ad. delta Rb gene transfer might be an efficient approach to prevent neointima formation in human saphenous vein grafts.
Martine L Lamfers; Marjanka C Aalders; Jos M Grimbergen; Margreet R de Vries; Mark M Kockx; Victor W van Hinsbergh; Paul H Quax
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Vascular pharmacology     Volume:  39     ISSN:  1537-1891     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2003-10-21     Completed Date:  2003-11-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  293-301     Citation Subset:  IM    
Gaubius Laboratory, TNO-PG, P.O. Box 2215, 2301 CE Leiden, The Netherlands.
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MeSH Terms
Adenoviridae / genetics*
Cell Division / physiology
Cells, Cultured
Coronary Artery Bypass*
Graft Occlusion, Vascular / genetics,  pathology*
Hyperplasia / pathology
Image Processing, Computer-Assisted
Muscle, Smooth, Vascular / cytology,  physiology*
Mutation / genetics*
Organ Culture Techniques
RNA, Messenger / biosynthesis,  genetics
Retinal Neoplasms / genetics*
Retinoblastoma / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Saphenous Vein / cytology,  growth & development
beta-Galactosidase / metabolism
Reg. No./Substance:
0/RNA, Messenger; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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