Background: Arterial restenosis after percutaneous transluminal angioplasty (PTA) significantly reduces its therapeutic efficacy in treating lower extremity atherosclerotic occlusive diseases (LEAOD). Early external X-ray external radiation has demonstrated positive effects on restenosis; however, effective dosing and the mechanism(s) underlying its efficacy remain unknown. This study explored the effect of early external X-ray radiation on preventing post-PTA restenosis in an iliac intimal injury model.
Methods: Twenty rabbits underwent iliac intimal injury via PTA and received five different radiation doses: 0 Gy (n=4), 3 Gy (n=4), 6 Gy (n=4), 9 Gy (n=4), and 12 Gy (n=4). Four rabbits were used as controls. All subjects were fed a high-fat diet prior to PTA and for an additional four-week period post-PTA and then sacrificed for immunohistochemical and Western blotting analysis.
Results: Arterial stenosis was significantly improved post-PTA. Alpha smooth muscle actin (α-SMA) expression in the 0 Gy to 9 Gy groups was significantly increased post-PTA. Cytochrome C (Cyt C) expression was significantly increased post-PTA and was positively correlated with radiation intensity. Proliferating cell nuclear antigen (PCNA) expression was significantly increased post-PTA with the 0 Gy group showing significantly higher expression than the 3 Gy group. No significant differences were found in CD34 levels between the groups.
Conclusions: Early external X-ray radiation at 6-24 Gy doses effectively restrained VSMC hyperplasia post-PTA, likely through inducing VSMC apoptosis via mitochondrial Cyt C release. However, this technique did not significantly affect the integrity of the vascular endothelium. Therefore, early external X-ray radiation shows promise in preventing post-PTA restenosis.
Keywords: PTA; Radiotherapy; VSMC; intimal injury; percutaneous transluminal angioplasty; restenosis; vascular smooth muscle.