Cellular effects of beta-particle delivery on vascular smooth muscle cellsand endothelial cells - A dose-response study

Background-Although endovascular radiotherapy inhibits neointimal hyperplas ia, the exact cellular alterations induced by beta irradiation remain to be elucidated. Methods and Results-We investigated in vitro the ability of P-32-labeled ol igonucleotides to alter (1) proliferation of human and porcine vascular smo oth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs), (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell mig ration, and (5) cell phenotype and morphological features. beta radiation s ignificantly reduced proliferation of VSMCs (ED50 1.10 Gy) and ECs (ED50 2. 15 Gy) in a dose-dependent manner. Exposure to beta emission interfered wit h cell cycle progression, with induction of G(0)/G(1) arrest in VSMCs, with out evidence of cell viability alteration, apoptosis, or ultrastructural ch anges. This strategy also proved to efficiently inhibit VSMC migration by 8 0% and induce contractile phenotype appearance, as shown by the predominanc e of alpha-actin immunostaining in beta-irradiated cells compared with cont rol cells. Conclusions-P-32-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. beta irradiation-induced G(1) arrest was not associated with cytotoxicity and apoptosis, thus demonstrat ing a potent cytostatic effect of beta-based therapy. This effect, coupled to that on VSMC migration inhibition and the appearance of a contractile ph enotype, reinforced the potential of ionizing radiation to prevent neointim a formation after angioplasty.