Document Detail


Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries.
MedLine Citation:
PMID:  16023630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Dexamethasone-eluting stents are currently under evaluation to prevent post-angioplasty restenosis. The efficacy and safety of dexamethasone as an anti-restenotic agent is still unclear. We assess the effect of perivascular delivery of dexamethasone on vascular pathology in a mouse model of restenosis. METHODS AND RESULTS: In this study we investigate the ability of both systemic and local dexamethasone treatment to inhibit neointima formation after cuff placement around C57BL/6 mouse femoral artery. As in the clinical situation, systemic dexamethasone treatment shows adverse side effects in animals, including weight loss. In contrast, local delivery of dexamethasone using a drug-eluting polymer cuff inhibits neointima formation and has no systemic adverse effects. Pathobiological examination of the experimental arteries, however, reveals a dose-dependent medial atrophy, a reduction in vascular smooth muscle cells and collagen content, an increase in apoptotic cell count and disruption of the internal elastic lamina. CONCLUSIONS: Our results demonstrate that although local dexamethasone delivery is effective as an inhibitor for neointima formation, it is dose-dependently associated with adverse vascular morphological changes pointing to a loss of vascular integrity.
Authors:
Nuno M M Pires; Abbey Schepers; Barend L van der Hoeven; Margreet R de Vries; Lianne S M Boesten; J Wouter Jukema; Paul H A Quax
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-07-15
Journal Detail:
Title:  Cardiovascular research     Volume:  68     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-08     Completed Date:  2006-05-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  415-24     Citation Subset:  IM    
Affiliation:
TNO-Quality of Life, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Transluminal, Percutaneous Coronary
Animals
Anti-Inflammatory Agents / administration & dosage*,  therapeutic use
Apoptosis / drug effects
Cell Proliferation / drug effects
Collagen / analysis
Coronary Disease / therapy
Coronary Restenosis / prevention & control*
Dexamethasone / administration & dosage*,  therapeutic use
Femoral Artery / pathology*
Male
Mice
Mice, Inbred C57BL
Models, Animal
Muscle, Smooth, Vascular / pathology
Stents*
Tunica Intima / pathology*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 50-02-2/Dexamethasone; 9007-34-5/Collagen
Comments/Corrections
Comment In:
Cardiovasc Res. 2005 Dec 1;68(3):350-2   [PMID:  16242679 ]

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


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