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Published Online
on February 16, 2004

Circulation. 2004
Published online before print February 16, 2004, doi: 10.1161/01.CIR.0000117404.65853.AF
A more recent version of this article appeared on March 2, 2004
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Submitted on July 11, 2003
Revised on October 17, 2003
Accepted on October 28, 2003

Reoxygenation of Hypoxic Coronary Smooth Muscle Cells Amplifies Growth-Retarding Effects of Ionizing Irradiation

Amina Arab MD, Thorsten Grumann MD, Roland Guttenberger MD, Christoph Bode MD, and Christoph Hehrlein MD*

From the Departments of Cardiology (A.A., T.G., C.B., C.H.) and Radiotherapy (R.G.), University of Freiburg, Germany.

* To whom correspondence should be addressed. E-mail: hehrlein{at}med1.ukl.uni-freiburg.de.

Background--Hypoxic human coronary smooth muscle cells (HCSMCs) are possible targets for brachytherapy to prevent restenosis after percutaneous transluminal coronary angiography. It is unclear whether growth kinetics and gene expression of these cells undergoing {gamma}-irradiation are changed by reoxygenation.

Methods and Results--Hypoxic (H) and hypoxia-reoxygenated (H-R) HCSMCs were irradiated with {gamma}-radiation at single doses of 4, 8, and 16 Gy using a 60Co-source. Vascular endothelial growth factor gene expression of HCSMCs was dramatically suppressed in H-R versus H cells independent of the radiation dose (15±7% versus 2183±2023%, P<0.01, H-R versus H cells). An oxygen enhancement ratio of 1.8 was calculated after irradiation from the retarded growth of H-R versus hypoxic HCSMCs. Production of reactive oxygen species by HCSMCs after irradiation increased by 15±2% in H-R cells versus 7±1% in H cells (P<0.05).

Conclusions--Reoxygenation of hypoxic HCSMCs markedly amplifies growth-retarding effects of ionizing irradiation. On the basis of these findings, oxygenating radiosensitizers should be analyzed with regard to suitability for coronary brachytherapy to prevent restenosis.


Key words: hypoxia • muscle, smooth • restenosis