Restenosis remains a significant clinical problem associated with coronary artery revascularization despite the recent advances using stents. Studies with rodents have established that platelet-derived growth factor (PDGF), a potent chemotatic and mitogenic agent for vascular smooth muscle cells, is a key mediator of lesion formation following vascular injury. To explore this hypothesis in a more clinically relevant model, we examined the effect of neutralizing anti-beta PDGF receptor (PDGFR) MoAb 2A1E2 on neointima formation in non-human primates. Carotid arteries were injured by endarterectomy and femoral arteries by balloon dilation; by 7 days both induced cell proliferation and the upregulation of beta PDGFR, which were determined immumohistochemically. PDGFR staining was limited to the luminal region of the media, the small areas of neointima and adventitia, as were nearly all proliferating cells. After 30 days, a concentric neointima that stained strongly for PDGFR had formed in the carotid and femoral arteries. Treatment of baboons with MoAb 2A1E2 for 6 days following injury caused a reduction in neointima formation of 29% (p<0.001) and 44% (p<0.0001) at the site of carotid endarterectomy or femoral balloon dilation, respectively, when measured at 30 days. These findings suggest that PDGFR antagonists may have therapeutic utility for preventing clinical restenosis.
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