プロブコール前投与,プラバスタチンによる血清脂質値低下によるPTCA術後再狭窄予防とその作用機序

Abstract

We previously reported a clinical study in which (1) Probucol prevented restenosis after coronary angioplasty and (2) Pravastatin reduced the risk of restenosis associated with plasma cholesterol concentration. To examine these mechanism, we analyzed the effect of probucol and pravastatin on the intimal proliferation, the cellular makeup of lesion and the expression of PDGF after balloon injury in rabbits. Probucol study: Probucol was given orally 1.3 g/day from 2 weeks prior to carotid balloon injury to the time of killing (2 or 4 weeks after balloon injury). Probucol remarkably decreased intimal area by 70%, the number of Smooth Muscle Cell (SMC) and Proliferating Cell Nuclear Antigen (PCNA)-labeled cells in the intima. The expression of PDGF-A mRNA was markedly suppressed with probucol treatment. However, probucol did not suppress SMemb expression. SMemb is a good molecular marker for de-differentiated SMC. Probucol is effective in preventing SMC proliferation, which is possibly due to a decrease in the expression of PDGF.Pravastatin study: Pravastatin was received orally 20mg/day with 0.5% cholestrol diet 2 weeks before iliac balloon injury. After 2 or 4 weeks, the rabbits were killed. Pravastatin reduced plasma cholesterol concentration, neointimal macrophage content and intimal area. The neointimal area was related to macrophage content. Moreover, macrophage content was correlated to plasma cholesterol level. Pravastatin effectively inhibits myointimal proliferation, which may be partly explained by its hypocholesterolemic activity.