Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury.
OBJECTIVE
We sought to evaluate the effects of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on vascular smooth muscle cell (VSMC) proliferation in vitro and neointimal formation in vivo after vascular injury.


BACKGROUND
Neointimal hyperplasia after vascular injury is responsible for restenosis after arterial stenting, whereas arterial remodeling and neointimal formation are the causes of restenosis after percutaneous transluminal coronary angioplasty.


METHODS
We assessed the effect of simvastatin on in vitro VSMC proliferation. To study the effects of simvastatin in vivo, balloon injury and stent deployment were performed in the common carotid artery of rats. Neointimal area was measured two weeks later in the balloon injury model and three weeks after stent deployment.


RESULTS
Simvastatin markedly inhibits VSMC proliferation in vitro. In vivo, simvastatin reduced, in a dose-dependent manner, the neointimal area and the neointima-media ratio after balloon injury from 0.266 +/- 0.015 mm2 to 0.080 +/- 0.026 mm2 and from 1.271 +/- 0.074 to 0.436 +/- 0.158 (p < 0.001 vs. control rats) at the highest dose. Simvastatin also significantly reduced the neointimal formation and the neointima-media ratio after stenting from 0.508 +/- 0.035 mm2 to 0.362 +/- 0.047 mm2 (p < 0.05 vs. control rats) and from 2.000 +/- 0.136 to 1.374 +/- 0.180 (p < 0.05 vs. control rats). The vessel thrombosis rate after stent deployment was 30% in the control group and 11.1% in the treated group (p = NS). Moreover, the systemic administration of simvastatin did not affect hepatic and renal functions, blood pressure or heart rate.


CONCLUSIONS
Simvastatin potently inhibits VSMC proliferation in vitro and reduces neointimal formation in a rat model of vascular injury.
Indolfi
C
C
Division of Cardiology, University Federico II, Naples, Italy. Indolfi@unina.it
Cioppa
A
A
Stabile
E
E
Di Lorenzo
E
E
Esposito
G
G
Pisani
A
A
Leccia
A
A
Cavuto
L
L
Stingone
A M
AM
Chieffo
A
A
Capozzolo
C
C
Chiariello
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D006083:Graft Occlusion, Vascular / Q000473:pathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D019821:Simvastatin / Q000494:pharmacology*; D015607:Stents; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin