The present study examined the effects of
prasugrel in a mouse model of
thrombosis-induced neointimal
hyperplasia. Following
carotid artery injury by application of
ferric chloride solution,
thrombus formation was assessed on Day 1 and neointimal thickening was assessed on Day 21. Single administrations of
prasugrel at 0.3-3mg/kg (p.o.) resulted in a dose-related and sustained inhibition of
ADP-induced platelet aggregation through 24h. Single and multiple (1 and 3 weeks) administration of
prasugrel (3mg/kg loading and 1mg/kg/day maintenance doses) resulted in a marked inhibition of neointimal thickening in the injured artery. In the dose-response study, a single administration of
prasugrel at 0.3-3mg/kg (p.o.) dose-relatedly inhibited
thrombus formation and neointimal thickening on Days 1 and 21, respectively. The degree of neointimal
hyperplasia in the injured artery correlated significantly with the
thrombus indices, time to occlusion and patency rate. To explore possible mechanisms of inhibition of neointimal
hyperplasia by
prasugrel,
mRNA expression levels of inflammatory and
fibrosis markers were determined in injured arteries.
Prasugrel treatment resulted in reduced MCP-1,
ICAM-1 and TGF-β
mRNA levels on Day 2 (24h after the injury) and Day 8 (1 week after the injury) in the target arteries. In conclusion, we found that a single oral loading dose of
prasugrel markedly prevented neointimal
hyperplasia by inhibiting platelet activation and
thrombus formation and was associated with inhibition of the expression of inflammatory and
fibrosis markers, including MCP-1,
ICAM-1 and TGF-β, in the injured arteries.