Document Detail


A new intra-arterial delivery platform for pro-arteriogenic compounds to stimulate collateral artery growth via transforming growth factor-beta1 release.
MedLine Citation:
PMID:  17659203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of this study was to develop a cytokine-eluting stent to stimulate collateral artery growth (arteriogenesis) in the peripheral circulation of the rabbit via local transforming growth factor (TGF)-beta1 release. BACKGROUND: The stimulation of arteriogenesis with cytokines is a potential new treatment option for patients suffering from vascular occlusive diseases. However, the lack of a delivery platform for continuous intra-arterial application of pro-arteriogenic compounds has hampered the clinical implementation of this promising therapeutic strategy. METHODS: Different polymer coatings were tested regarding their suitability for cytokine release. Fifty-four rabbits underwent implantation of bare-metal stents (BMS), polymer-only coated stents (PDLLA), polymer-coated TGF-beta1-eluting stents (TGF) in the iliac artery, or bolus infusion of TGF-beta1 and subsequent femoral artery ligation. Collateral artery growth was assessed with fluorescent microspheres, angiography, and histological quantification of the proliferation marker Ki67. In-stent neointima formation was measured in histological sections of plastic-embedded stents. RESULTS: A TGF-beta1-loaded coating based on poly(D,L-lactide) released up to 2.4 microg active TGF-beta1 over a period of 24 h. Perfusion measurements revealed a significant increase in collateral conductance after TGF-beta1 stent implantation compared with the control groups ([ml/min/100 mm Hg] BMS: 47.8 +/- 2.5; PDLLA: 44.1 +/- 3.9; TGF: 91.3 +/- 32.6). Bolus infusion of TGF-beta1 had no effect. Collateral arteries showed a higher proliferation activity in the TGF-treated group. At 7 days, no significant difference in in-stent neointima formation was observed. CONCLUSIONS: We first describe the use of a cytokine-releasing stent to stimulate collateral artery growth. These results show that intra-arterial cytokine-releasing devices might serve as a novel platform for the delivery of compounds affecting biological processes downstream of the site of implantation.
Authors:
Sebastian Grundmann; Niels van Royen; Gerard Pasterkamp; Nieves Gonzalez; Edze J Tijsma; Jan J Piek; Imo E Hoefer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-10
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  50     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-30     Completed Date:  2007-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  351-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiology, AMC, University of Amsterdam, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Absorbable Implants
Angiogenesis Inducing Agents / administration & dosage*
Animals
Arterial Occlusive Diseases / drug therapy*,  physiopathology
Collateral Circulation / drug effects*,  physiology
Disease Models, Animal
Drug Delivery Systems
Neovascularization, Physiologic / drug effects*,  physiology
Polymers
Rabbits
Stents*
Transforming Growth Factor beta1 / administration & dosage*,  secretion*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Polymers; 0/Transforming Growth Factor beta1

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


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