Salu KJ, Bosmans JM, Huang Y, Hendriks M,
Verhoeven M, Levels A, Cooper S, De Scheerder IK, Vrints CJ,
Bult H.Effects of cytochalasin D -eluting
stents on intimal hyperplasia in a porcine coronary artery
model.
Cardiovasc Res. 2006 Feb 1;69(2):536-44. Epub 2005 Dec
28.
Division of Cardiology, University of Antwerp,
Universiteitsplein 1, B-2610 Wilrijk, Belgium.
OBJECTIVE: To investigate whether cytochalasin D-eluting
stents (CDES) suppress intimal hyperplasia in porcine coronary
arteries and to compare the efficacy of paclitaxel and
cytochalasin D as inhibitors of vascular smooth muscle cell
(SMC) proliferation and platelet aggregation in vitro. METHODS:
Rabbit platelet-rich plasma and SMC cultures derived from rabbit
aortas were exposed to 10(-8)-10(-5) M cytochalasin D or
paclitaxel. Stents directly coated with 2 microg cytochalasin D
(low-dose CDES, n=12) and bare stents (n=12) were randomly
deployed in the right and left coronary artery of 12 pigs. Six
weeks later, neointima was studied using quantitative coronary
angiography (QCA) and morphometry. To examine a ten-fold higher
dose, polybutyl methacrylate/polyvinyl acetate-coated stents
were loaded with 20 microg cytochalasin D. High-dose CDES (n=10)
and polymer-only stents (n=11) were deployed in 11 pigs.
RESULTS: After 7 days, cytochalasin D (IC(50) 9.9+/-0.4 10(-8)
M) and paclitaxel (IC(50) 1.1+/-0.4 10(-8) M) inhibited SMC
proliferation in vitro (n=4). In contrast, cytochalasin D
(10(-6)-10(-5) M, n=5), but not paclitaxel, attenuated platelet
shape change and aggregation induced by ADP. In vivo QCA showed
less late lumen loss in low-dose CDES (0.08+/-0.07 vs.
0.32+/-0.08 mm, P=0.05), but morphometry demonstrated only a
tendency toward a decreased intimal area. High-dose CDES
inhibited both late lumen loss (0.31+/-0.08 vs. 0.91+/-0.06 mm,
P<0.01) and intimal area (1.57+/-0.20 vs. 2.46+/-0.22 mm(2),
P<0.01). Immunohistochemistry revealed that CDES suppressed peri-strut
macrophage recruitment (CD68, P=0.04) and cell proliferation
(Ki67, P=0.03) as compared to polymer-only stents without
interfering with endothelial cell recovery or the density of
alpha-SMC actin staining. Thromboses or edge effects were not
observed in either study. CONCLUSIONS: CDES inhibited in-stent
hyperplasia. The reduction (39%) with 20 mug CDES was equivalent
to that reported for paclitaxel-eluting stents in pigs.
Interference with platelet aggregation, SMC migration, SMC
proliferation, and leukocyte recruitment could contribute to the
benefit. The data indicate that targeting of actin
microfilaments has a potential to suppress in-stent restenosis.
PMID: 16386237
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