Carvastatin suppresses intimal thickening of rabbit carotid artery after balloon catheter injury probably through the inhibition of vascular smooth muscle cell proliferation and migration
M. Komukai et al., Carvastatin suppresses intimal thickening of rabbit carotid artery after balloon catheter injury probably through the inhibition of vascular smooth muscle cell proliferation and migration, SC J CL INV, 59(3), 1999, pp. 159-166
Citations number
20
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION
In order to test whether a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
reductase inhibitor has an anti-atherogenic activity, the effects of carvas
tatin, a newly developed potent inhibitor, and pravastatin were examined on
the intimal thickening of the artery after the endothelial denudation indu
ced by balloon catheter injury. Rabbits were divided into four groups; cont
rol, pravastatin-treated (20 mg kg(-1) day(-1)) and two of carvastatin-trea
ted groups (10 or 20 mg kg(-1) day(-1)). Two weeks after balloon catheter i
njury, the areas of intima and media of the injured carotid arteries were d
etermined, and the ratios of intima to media (UM) were calculated as an ind
ex of intimal thickening. Average I/M ratios of the injured artery were 0.4
2 +/- 0.05 for control, 0.49 +/- 0.07 far pravastatin, 0.19 +/- 0.03 (10 mg
kg(-1) day(-1)) and 0.20 +/- 0.04 (20 mg kg(-1) day(-1)) for carvastatin-t
reated rabbits, respectively. Thus, carvastatin reduced UM ratio of the inj
ured artery to approximately half versus control, but pravastatin failed to
suppress the intimal thickening. For in vitro study, vascular smooth muscl
e cells (SMC) from rabbit aorta were explanted, then cultured, and the effe
cts of carvastatin on SMC migration and SMC proliferation were also examine
d. Carvastatin inhibited dose-dependently SMC migration and SMC proliferati
on with IC50 values of 0.5 mu M and 1 mu M, respectively. These inhibitory
effects of carvastatin were cancelled by the coexistence of mevalonate, a m
etabolite of cholesterol synthesis. Our results suggest that carvastatin ma
y be useful in rabbits as an anti-atherogenic drug by means of the inhibiti
on of SMC migaration or SMC proliferation.