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on May 13, 2002

Circulation. 2002
Published online before print May 13, 2002, doi: 10.1161/01.CIR.0000016048.03020.6C
A more recent version of this article appeared on May 21, 2002
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Submitted on December 31, 2001
Revised on February 27, 2002
Accepted on February 28, 2002

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, and 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.

* To whom correspondence should be addressed. 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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