title: Increased expression of macrophage colony-stimulating factor after coronary artery balloon injury is inhibited by intracoronary brachytherapy.
abstract: 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.
authors.affiliation: Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles, CA 90048-1865, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Finkelstein
authors.forename: Raj
authors.initials: R
authors.lastname: Makkar
authors.forename: Terence M
authors.initials: TM
authors.lastname: Doherty
authors.forename: Vijaya R
authors.initials: VR
authors.lastname: Vegesna
authors.forename: Pinky
authors.initials: P
authors.lastname: Tripathi
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bergman
authors.forename: Michael
authors.initials: M
authors.lastname: Fishbein
authors.forename: Joerg
authors.initials: J
authors.lastname: Hausleiter
authors.forename: Kaname
authors.initials: K
authors.lastname: Takizawa
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rukshin
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.forename: Tripathi B
authors.initials: TB
authors.lastname: Rajavashisth
mesh_terms: 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
chemical_list: D010975:Platelet Aggregation Inhibitors; D016173:Macrophage Colony-Stimulating Factor