An iron-binding exochelin prevents restenosis due to coronary artery balloon injury in a porcine model

Background-Vascular smooth muscle cell (VSMC) proliferation is a critical f actor in the neointima formation that causes restenosis after coronary angi oplasty (PTCA). Desferri-exochelin 772SM (D-EXO), a highly diffusible, lipo philic iron chelator secreted by Mycobacterium tuberculosis, inhibits proli feration of VSMCs in culture. We hypothesized that treatment with D-EXO wou ld inhibit neointima formation in balloon-injured vessels in vivo. Methods and Results-We subjected 24 pigs to overstretch coronary artery inj ury with standard PTCA balloons and then administered intramural injections of either D-EXO (n=14) or vehicle (n=10) through an Infiltrator catheter. Treatments were randomized, and the investigators were blinded with regard to treatment group until data analysis was completed. One month later, we e uthanized the pigs, excised the injured coronary segments, made multiple se ctions of each segment, and identified the site of maximal neointima format ion. An injury score based on the degree of disruption of the internal or e xternal elastic lamina or media was assigned. D-EXO reduced stenosis index (neointima area divided by the area within the internal elastic lamina), ad justed for injury score, by 47%. Neointima thickness was also reduced. Conclusions-D-EXO, injected intramurally, substantially inhibited formation of neointima in a porcine vascular injury model.