Abstract
Vascular smooth muscle cell proliferation and vascular homeostasis is thought to be regulated by nitric oxide and prostaglandins. We examined the effect of exogenous linsidomine, a NO releasing compound, in a model of balloon injury iliac arteries of rabbits. On the cellular levels NO can exert effects like cellular survival, growth and proliferation inhibition. Smooth muscle cell (SMC) proliferation was quantified as change of intima-media-ratio. Linsidomine injection or its vehicle was performed with an infusion-balloon catheter directly into the vessel wall. Balloon angioplasty resulted in a significant increase of intima-media-ratio during three weeks. Linsidomine treatment decreased the intima media ratio significantly (0.65±0.05 vs 1,2±0.2 intima-media-ratio, p<0.05). However, control vessels had an intima media ratio of 0.15±0.02. This effect was similar to NOS-2 transfected vessels following angioplasty. In in vitro experiments linsidomine inhibited significantly and dose-dependently rabbit smooth muscle cell proliferation measured by BrdU incorporation. Further linsidomine increased rate of apoptotic SMC's, however this effect was p53 independent. Simultaneous angioplasty of the rabbit iliac artery and direct injection of linsidomine into the vessel wall seem to be an effective strategy to reduce neointima formation. Despite single administration, local application of linsidomine resulted in potent inhibition of intima proliferation.
Published Version
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