Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery

Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery

The antineoplastic compound paclitaxel (Taxol) causes an increased assembly of extraordinarily stable microtubules. The present study was designed to characterize the effects of paclitaxel on proliferation and migration of human arterial smooth muscle cells (haSMCs) in vitro and on neointima formati...

Full description

Saved in:
Bibliographic Details
Published in:Circulation (New York, N.Y.) Vol. 96; no. 2; pp. 636 - 645
Main Authors: AXEL, D. I, KUNERT, W, KARSCH, K. R, GÖGGELMANN, C, OBERHOFF, M, HERDEG, C, KÜTTNER, A, WILD, D. H, BREHM, B. R, RIESSEN, R, KÖVOKER, G
Format: Journal Article
Language:English
Published: Hagerstown, MD Lippincott Williams & Wilkins 15-07-1997
American Heart Association, Inc
Subjects:
Animals
Biological and medical sciences
Cardiovascular system
Carotid Arteries
Cell Division - drug effects
Cell Movement - drug effects
Cells, Cultured
Drug Delivery Systems
Humans
Male
Medical sciences
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - pathology
Paclitaxel - administration & dosage
Pharmacology. Drug treatments
Rabbits
Vascular wall
Human
Cell proliferation
Cell culture
Immunocytochemistry
Treatment efficiency
Migration
Rabbit
Smooth muscle
Lagomorpha
In vitro
Artery
Pathology
In vivo
Vertebrata
Chemotherapy
Mammalia
Treatment
Animal
Taxane derivatives
Paclitaxel
Antimitotic
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The antineoplastic compound paclitaxel (Taxol) causes an increased assembly of extraordinarily stable microtubules. The present study was designed to characterize the effects of paclitaxel on proliferation and migration of human arterial smooth muscle cells (haSMCs) in vitro and on neointima formation in an in vivo experimental rabbit model. Both monocultures of haSMCs and cocultures with human arterial endothelial cells (haECs) were used. Cell growth after 4, 8, and 14 days was determined in the absence or presence of platelet-derived growth factor-AB (PDGF-AB), basic fibroblast growth factor (bFGF), or thrombin. Nonstop paclitaxel exposure, as well as single-dose applications of paclitaxel for 24 hours or even 20 minutes (0.1 to 10.0 micromol/L), caused a complete and prolonged inhibition of haSMC growth up to day 14, with an IC50 of 2.0 nmol/L. Mitogens or cocultures with stimulating haECs did not significantly attenuate paclitaxel-induced effects. Immunohistochemistry showed characteristic cytoskeletal changes predominantly in the microtubule network. Additionally, in 20 male New Zealand White rabbits, intimal plaques were produced by electrical stimulation. In 10 animals, paclitaxel was locally applied by use of microporous balloons. Histologically, the intima wall area, wall thickness, and degree of stenosis were reduced significantly in paclitaxel-treated animals compared with controls. Our data show that paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens. Furthermore, paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The long-lasting effect after just several minutes' exposure time makes this lipophilic substance a promising candidate for local antiproliferative therapy of restenosis.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.96.2.636