Inhibitory effect of recombinant TGFalpha-PE40 on neointimal proliferation after arterial balloon injury

To investigate inhibitory effects of recombinant transforming growth factor alpha-Pseudomonas exotoxin 40 fusion protein (TGFalpha-PE40; TP40) on neointimal proliferation after arterial balloon injury.

Forty male rabbits fed a cholesterol rich diet were randomly divided into TP40 15 microg, 30 microg, 60 microg, physiologic saline control, and normal artery groups (n=8). Rabbits in the treatment groups were treated by local administration of TP40 (15 microg, 30 microg, and 60 microg per rabbit) 24 h postinjury, and those in the control group were treated by physiologic saline 24 h postinjury. Remained 8 rabbits in normal artery group were treated by TP40 (60 microg). Optical microscope, electron microscope, and computer image analysis were used to study arterial segments 2 weeks after treatment.

Irregular thickening of the arterial intima, large amounts of smooth muscle cells (SMC) within the neointima, and stenosis of the arterial cavity were observed in the physiologic saline control group. Great inhibition of intimal proliferation and prevention of stenosis of the arterial cavity were observed in the TP40 treated groups that were examined 2 weeks postinjury by optical microscope. The uninjured carotids were histologically normal. Lots of destructural and necrotic SMC were observed in media in TP40 60 microg group by electron microscope. Computer image analysis showed that the neointimal area of the TP40-treated groups was markedly smaller than that of the saline control group (P < 0.01).

Recombinant TP40 greatly inhibited neointimal proliferation after arterial balloon injury.