Inhibitory effect of recombinant TGF(alpha)-PE40 on neointimal proliferation after arterial balloon injury

AIM: To investigate inhibitory effects of recombinant transforming growth f actor alpha -Pseudomonas exotoxin 40 fusion protein (TGF(alpha)-PE40; TP40) on neointimal proliferation after arterial balloon injury. METHODS: Forty male rabbits fed a cholesterol rich diet were randomly divided into TP40 15 mug, 30 mug, 60 mug, physiologic saline control, and normal artery groups (n = 8). Rabbits in the treatment groups were treated by local administrati on of TP40 (15 mug, 30 mug, and 60 mug per rabbit) 24 h postinjury, and tho se in the control group were treated by physiologic saline 24 h postinjury. Remained 8 rabbits in normal artery group were treated by TP40 (60 mug). O ptical microscope, electron microscope, and computer image analysis were us ed to study arterial segments 2 weeks after treatment. RESULTS: Irregular t hickening of the arterial intima, large amounts of smooth muscle cells (SMC ) within the neointima, and stenosis of the arterial cavity were observed i n the physiologic saline control group. Great inhibition of intimal prolife ration and prevention of stenosis of the arterial cavity were observed in t he TP40-treated groups that were examined 2 weeks postinjury by optical mic roscope. The uninjured carotids were histologically normal. Lots of destruc tural and necrotic SMC were observed in media in TP40 60 mug group by elect ron microscope. Computer image analysis showed that the neointimal area of the TP40-treated groups was markedly smaller than that of the saline contro l group (P < 0.01). CONCLUSION: Recombinant TP40 greatly inhibited neointim al proliferation after arterial balloon injury.