Increased expression of macrophage colony-stimulating factor after coronary artery balloon injury is inhibited by intracoronary brachytherapy.

Abstract

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). 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). 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.