Document Detail


Sustained improvement in perfusion and flow reserve after temporally separated delivery of vascular endothelial growth factor and angiopoietin-1 plasmid deoxyribonucleic Acid.
MedLine Citation:
PMID:  22464261     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: The aim of this study was to compare temporally separated vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 delivery with concomitant delivery or single VEGF delivery, for therapeutic angiogenesis in chronic ischemia.
BACKGROUND: Single gene delivery of VEGF results in immature neovessels that ultimately regress. Endogenously, VEGF acts early to initiate angiogenesis, whereas Ang-1 acts later to induce vessel maturation. Timing VEGF and Ang-1 gene delivery to mimic endogenous angiogenesis might be more effective for sustained neovascularization.
METHODS: Unilateral hindlimb ischemia was induced in 170 rats. Ultrasound-mediated gene delivery was performed with cationic microbubbles and plasmid deoxyribonucleic acid. Groups included VEGF at 2 weeks, VEGF/Ang-1 at 2 weeks, VEGF at 2 weeks with Ang-1 at 4 weeks, and untreated control subjects. At 2, 4, and 8 weeks after ligation, blood flow and flow reserve (FR) were assessed by contrast-enhanced ultrasound. Vascular density, organization, and supporting cell coverage were assessed by fluorescent microangiography and immunohistochemistry.
RESULTS: In untreated control subjects, blood flow, FR, and vessel density remained reduced. The VEGF delivery improved flow and vessel density at 4 weeks; however, FR remained low, supporting cell coverage was poor, and flow and vessel density regressed by 8 weeks. The VEGF/Ang-1 co-delivery marginally increased flow and vessel density; however, FR and supporting cell coverage improved. After temporally separated VEGF and Ang-1 delivery, blood flow, vessel density, and FR increased and were sustained, with improved pericyte coverage at 8 weeks.
CONCLUSIONS: In conclusion, temporally separated VEGF and Ang-1 gene therapy results in sustained and functional neovascularization.
Authors:
Alexandra H Smith; Michael A Kuliszewski; Christine Liao; Dmitriy Rudenko; Duncan J Stewart; Howard Leong-Poi
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  59     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-02     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1320-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Division of Cardiology, Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
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