Effects of ionizing irradiation on vascular smooth muscle cells and matrix: Implications for inhibiting post-interventional restenosis

Background: Ionizing irradiation (gamma-RT) has been shown to inhibit post- interventional vascular restenosis but there is limited understanding about the underlying mechanisms. Methods: gamma-RT (10, 20 Gy) were applied to vascular smooth muscle cells (SMC) in vitro and to cell culture plates coated with extracellular matrix. Cell viability (tetrazolium salt), proliferation (H-3-thymidine), collagen synthesis (H-3-proline), collagen I mRNA expression (RT-PCR) and condition ed media experiments were used to asses gamma-RT effects on the vascular fi broproliferative response. Results: gamma-RT reduced cellular proliferation to 24% +/- 2.7 (10 Gy) and 31% +/- 3.0 (20 Gy), controls: 100% +/- 5.3; p < 0.0001, but did not affec t metabolic activity. Stimulation with calf serum increased mitochondrial a ctivity (162% +/- 8.2 (10 Gy) and 150% +/- 9.7 (20 Gy); p < 0.0001). Collag en synthesis decreased after 7 days (55% +/- 5.5, controls: 100% +/- 8.4), but was also stimulable with calf serum (81% +/- 5.8; p < 0.001). Collagen I mRNA expression did not change in all groups. gamma-RT did not affect cel l and matrix associated growth factors. Conclusions: These data suggest that gamma-RT may inhibit restenosis by ind ucing growth arrest of smooth muscle cells. However, irradiated cells conti nue to respond to growth factor stimulation and can increase their collagen production. gamma-RT with in vivo used doses does not interfere with growt h factors leading to the vascular fibroproliferative response.