Document Detail


Reduction of intimal hyperplasia in injured rat arteries promoted by catheter balloons coated with polyelectrolyte multilayers that contain plasmid DNA encoding PKCδ.
MedLine Citation:
PMID:  23069712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
New therapeutic approaches that eliminate or reduce the occurrence of intimal hyperplasia following balloon angioplasty could improve the efficacy of vascular interventions and improve the quality of life of patients suffering from vascular diseases. Here, we report that treatment of arteries using catheter balloons coated with thin polyelectrolyte-based films ('polyelectrolyte multilayers', PEMs) can substantially reduce intimal hyperplasia in an in vivo rat model of vascular injury. We used a layer-by-layer (LbL) process to coat the surfaces of inflatable catheter balloons with PEMs composed of nanolayers of a cationic poly(β-amino ester) (polymer 1) and plasmid DNA (pPKCδ) encoding the δ isoform of protein kinase C (PKCδ), a regulator of apoptosis and other cell processes that has been demonstrated to reduce intimal hyperplasia in injured arterial tissue when administered via perfusion using viral vectors. Insertion of balloons coated with polymer 1/pPKCδ multilayers into injured arteries for 20 min resulted in local transfer of DNA and elevated levels of PKCδ expression in the media of treated tissue three days after delivery. IFC and IHC analysis revealed these levels of expression to promote downstream cellular processes associated with up-regulation of apoptosis. Analysis of arterial tissue 14 days after treatment revealed polymer 1/pPKCδ-coated balloons to reduce the occurrence of intimal hyperplasia by ~60% compared to balloons coated with films containing empty plasmid vectors. Our results demonstrate the potential therapeutic value of this nanotechnology-based approach to local gene delivery in the clinically important context of balloon-mediated vascular interventions. These PEM-based methods could also prove useful for other in vivo applications that require short-term, surface-mediated transfer of plasmid DNA.
Authors:
Shane L Bechler; Yi Si; Yan Yu; Jun Ren; Bo Liu; David M Lynn
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-13
Journal Detail:
Title:  Biomaterials     Volume:  34     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-10-29     Completed Date:  2013-03-26     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  226-36     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Balloon, Coronary / adverse effects*
Animals
Carotid Arteries / drug effects,  pathology
Carotid Artery Injuries / etiology*,  pathology,  prevention & control*
Coated Materials, Biocompatible / pharmacology*
DNA / metabolism*
Electrolytes / chemistry
Fluorescent Antibody Technique
Gene Transfer Techniques
Hyperplasia
In Situ Nick-End Labeling
Male
Microscopy, Fluorescence
Plasmids / metabolism
Polymers / chemistry
Protein Kinase C-delta / metabolism*
Rats
Rats, Sprague-Dawley
Tunica Intima / drug effects,  pathology*
Grant Support
ID/Acronym/Agency:
R01 EB006820/EB/NIBIB NIH HHS; R01 EB006820/EB/NIBIB NIH HHS; R01 HL081424/HL/NHLBI NIH HHS; R01 HL081424/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Coated Materials, Biocompatible; 0/Electrolytes; 0/Polymers; 9007-49-2/DNA; EC 2.7.11.13/Protein Kinase C-delta
Comments/Corrections

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