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).


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.
Finkelstein
Ariel
A
Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, CA 90048-1865, USA.
Makkar
Raj
R
Doherty
Terence M
TM
Vegesna
Vijaya R
VR
Tripathi
Pinky
P
Liu
Ming
M
Bergman
Jonathan
J
Fishbein
Michael
M
Hausleiter
Joerg
J
Takizawa
Kaname
K
Rukshin
Vladimir
V
Shah
Prediman K
PK
Rajavashisth
Tripathi B
TB
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D001918:Brachytherapy; D002455:Cell Division / Q000528:radiation effects; D023903:Coronary Restenosis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D013552:Swine; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology / Q000528:radiation effects
D010975:Platelet Aggregation Inhibitors; D016173:Macrophage Colony-Stimulating Factor