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(Circulation. 2002;105:2411.)
© 2002 American Heart Association, Inc.

Basic Science Reports

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

Ariel Finkelstein, MD; Raj Makkar, MD; Terence M. Doherty, BA; Vijaya R. Vegesna, PhD; Pinky Tripathi, BS; Ming Liu, MD; Jonathan Bergman, BS; Michael Fishbein, MD; Joerg Hausleiter, MD; Kaname Takizawa, MD; Vladimir Rukshin, MD; Prediman K. Shah, MD; Tripathi B. Rajavashisth, PhD

From the Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, and Departments of Pathology and Laboratory Medicine, UCLA School of Medicine (M.F.), Los Angeles, Calif.

Correspondence to Tripathi B. Rajavashisth, PhD, Atherosclerosis Research Center, Davis Research Bldg, Room 1062, Division of Cardiology, Cedars-Sinai Medical Center, UCLA School of Medicine, 8700 Beverly Blvd, Los Angeles, CA 90048-1865. E-mail rajavashisth{at}cshs.org

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 ³²P 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 mm²; P<0.001 versus control), but this was reduced by ICBT (1.4±0.4 mm²; 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.

Key Words: muscle, smooth • radioisotopes • cells • restenosis • proliferation

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