Increased Expression of Macrophage Colony–Stimulating Factor After Coronary Artery Balloon Injury Is Inhibited by Intracoronary Brachytherapy

Background — The mechanisms underlying the reduced neointimal proliferation (NP) by intracoronary brachytherapy (ICBT) are unknown. We hypothesized that ICBT inhibits NP by reducing expression of macrophage colony–stimulating factor (M-CSF). Methods and Results — Thirty coronary arteries from 10 pigs were divided into 3 groups of 10 each: control (C), balloon injury (BI), and BI followed by ICBT (16 Gy at 0.5-mm tissue depth with a 32 P balloon system). Pigs were killed at 24 hours (n=3) and at 7 (n=4) and 14 (n=3) days. Expression of M-CSF was assessed by Western blot, ELISA, and quantitative immunostaining. Persistently increased levels of M-CSF after BI (to 1.4±0.2 nmol/L [ELISA] and 29.4±4.9% of cross-sectional area stained [immunocytochemistry]; P < 0.001 versus control for both) were observed in the injured arteries. Treatment of BI arteries with ICBT reduced M-CSF expression compared with BI alone (to 0.7±0.1 nmol/L [ELISA] and 13.5±2.9% of cross-sectional area stained [immunocytochemistry]; P <0.001 versus BI and P =NS versus control for both) and remained similar to control M-CSF expression for the 14-day study period. Neointimal thickness increased after BI (to 4.8±2.9 mm 2 ; P <0.001 versus control), but this was reduced by ICBT (1.4±0.4 mm 2 ; P <0.001 versus BI). Conclusions — In porcine coronary arteries, BI is associated with increased expression of M-CSF and NP, but neither occurs after ICBT. The beneficial effects of ICBT on NP involve inhibition of M-CSF expression.