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(Circulation. 1999;99:1477-1484.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Cellular Effects of ß-Particle Delivery on Vascular Smooth Muscle Cells and Endothelial Cells

A Dose-Response Study

Jeannette Fareh, PhD; Rémi Martel, PhD; Pouneh Kermani, PhD; Guy Leclerc, MD

From the Laboratory of Molecular Cardiology, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.

Correspondence to Guy Leclerc, MD, Laboratory of Molecular Cardiology, CHUM, 1560, Sherbrooke East, Montreal, Quebec, Canada, H2L4 M1.

Background—Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact cellular alterations induced by ß irradiation remain to be elucidated.

Methods and Results—We investigated in vitro the ability of ³²P-labeled oligonucleotides to alter (1) proliferation of human and porcine vascular smooth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs), (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell migration, and (5) cell phenotype and morphological features. ß radiation significantly reduced proliferation of VSMCs (ED₅₀ 1.10 Gy) and ECs (ED₅₀ 2.15 Gy) in a dose-dependent manner. Exposure to ß emission interfered with cell cycle progression, with induction of G₀/G₁ arrest in VSMCs, without evidence of cell viability alteration, apoptosis, or ultrastructural changes. This strategy also proved to efficiently inhibit VSMC migration by 80% and induce contractile phenotype appearance, as shown by the predominance of -actin immunostaining in ß-irradiated cells compared with control cells.

Conclusions—³²P-labeled oligonucleotide was highly effective in inhibiting proliferation of both VSMCs and ECs in a dose-dependent fashion, with ECs showing a higher resistance to these effects. ß irradiation–induced G₁ arrest was not associated with cytotoxicity and apoptosis, thus demonstrating a potent cytostatic effect of ß-based therapy. This effect, coupled to that on VSMC migration inhibition and the appearance of a contractile phenotype, reinforced the potential of ionizing radiation to prevent neointima formation after angioplasty.

Key Words: restenosis • radiation • angioplasty • cells • endothelium • apoptosis

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