© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Effects of local all-trans-retinoic acid delivery on experimental atherosclerosis in the rabbit carotid artery
aDivision of Cardiology, Department of Medicine, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany
bInstitute for Medical Information Processing, University of Tuebingen, Otfried-Mueller-Str. 10, D-72076 Tuebingen, Germany
cDepartment of Cardiology, Bristol Heart Institute, University of Bristol, Bristol, UK
christian.herdeg{at}med.uni-tuebingen.de
* Corresponding author. Tel.: +49-7071-298-2712; fax: +49-7071-293-169.
Background: Retinoids regulate a variety of biological processes and play an important role in cell differentiation and proliferation. All-trans retinoid acid (atRA) is known to inhibit smooth muscle cell growth and thus is supposed to have favorable effects on the incidence of restenosis after percutaneous coronary interventions. The broad biological spectrum, however, leads to numerous severe side effects which limit the clinical use of a systemic application of atRA. In order to avoid systemic side effects, local delivery of atRA is preferable. The aim of this study was to evaluate the effects of atRA on the response to injury in a second-injury model of experimental balloon angioplasty. Methods: After induction of a fibromuscular plaque in the right carotid artery of 40 New Zealand rabbits, 35 animals underwent balloon angioplasty of the preformed plaque formation. Subsequent local atRA delivery (10 ml, 10 µM) with the double-balloon catheter was performed in 15 animals. Five animals received vehicle only as sham controls, and five animals were solely electrostimulated, 15 animals served as control group with balloon angioplasty only. Vessels were excised 7 days (n=15) and 28 days (n=30) after intervention. Immunocytochemistry with antibodies against smooth muscle 
-actin and myosin, bromodeoxyuridine, macrophages, collagen I and III and von Willebrand factor was performed. Quantitative analysis was done by computerized morphometry. Results: After local atRA delivery in vivo, the extent of stenosis was markedly reduced with 21.7±8.3% (mean±S.D.) 4 weeks after intervention compared to 31.8±13.4% in balloon-dilated animals (P=0.0937). Both a reduced early neointimal proliferation (P=0.0002) and an increase in overall vessel diameter (4 weeks after intervention, P=0.0264) contributed to a limitation of restenosis in atRA-treated animals. Immunocytochemistry revealed a more intense -actin staining pattern after local atRA therapy indicating redifferentiating effects of atRA on vascular smooth muscle cells. Conclusions: Local delivery of atRA led to limitation of restenosis formation in this animal model. The concept of a local atRA therapy might be a promising way to exploit the potential of atRA for vascular indications while minimizing the severe side effects of systemic retinoid therapy.
KEYWORDS ANOVA, analysis of variance; AtRA, all-trans-retinoic acid; BD, balloon dilatation; BRDU, bromodeoxyuridine; LDD, local drug delivery; SMC, smooth muscle cell
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Camacho, C. Rodriguez, J. Salazar, J. Martinez-Gonzalez, J. Ribalta, J.-R. Escudero, L. Masana, and L. Vila Retinoic acid induces PGI synthase expression in human endothelial cells J. Lipid Res., August 1, 2008; 49(8): 1707 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Yokoyama, Y. Sato, T. Akaike, S. Ishida, J. Sawada, T. Nagao, H. Quan, M. Jin, M. Iwamoto, S. Yokota, et al. Maternal vitamin A alters gene profiles and structural maturation of the rat ductus arteriosus Physiol Genomics, September 11, 2007; 31(1): 139 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kada, T. Suzuki, K. Aizawa, T. Matsumura, N. Ishibashi, N. Suzuki, N. Takeda, Y. Munemasa, D. Sawaki, T. Ishikawa, et al. Acyclic Retinoid Inhibits Neointima Formation Through Retinoic Acid Receptor Beta-Induced Apoptosis Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1535 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Nicholls, G. J. Dusting, B. Cutri, S. Bao, G. R. Drummond, K.-A. Rye, and P. J. Barter Reconstituted High-Density Lipoproteins Inhibit the Acute Pro-Oxidant and Proinflammatory Vascular Changes Induced by a Periarterial Collar in Normocholesterolemic Rabbits Circulation, March 29, 2005; 111(12): 1543 - 1550. [Abstract] [Full Text] [PDF]
|
|