Different effects of photodynamic therapy and gamma-irradiation on vascular smooth muscle cells and matrix - Implications for inhibiting restenosis

gamma-Irradiation (gamma-RT) and photodynamic therapy (PDT) are known to in hibit intimal hyperplasia. The common mechanism is that both modalities pro duce free radicals, but unlike gamma-RT, PDT generates them through the abs orption of light by photosensitizers. The purpose of this in vitro study wa s to assess the differences that PDT and gamma-RT have on the fibroprolifer ative response after vascular injury by comparing their effects on vascular smooth muscle cells (SMCs) and on the extracellular matrix (ECM). Mitochon drial activity (tetrazolium salt), proliferation ([H-3]thymidine]thymidine incorporation), and the mechanisms of cell death (terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling [TUNEL] staining) were used to assess differences between PDT (100 J/cm(2)) and gamma-RT(10 or 20 Gy) on SMC injury. The different effects on bioregulatory molecules were in vestigated by quantitating the proliferation of SMCs cultured with conditio ned medium and on treated ECM. PDT of SMCs reduced proliferation and mitoch ondrial activity (0.5 +/- 0.75% and 1.7 +/- 4.25%, respectively, P<0.0001), whereas gamma-RT of SMCs decreased cell proliferation but did not affect m etabolic activity. Stimulation with calf serum of gamma-RT-treated SMCs did not affect proliferation but increased mitochondrial enzyme activity (160 +/- 11%, P<0.0005). The conditioned medium, derived from PDT- but not gamma -RT-treated SMCs, did not stimulate effector SMC proliferation compared wit h gamma-RT-treated SMCs(16 +/- 4.1% versus 80 +/- 16.8%, P<0.0001). Apoptos is was the principle cytotoxic mechanism after PDT, whereas gamma-RT cells were growth arrested but viable. PDT of the ECM reduced effector SMC prolif eration compared with controls and gamma-RT cells (18 +/- 6.5% versus 100 /- 17.7% and 84 +/- 8.9%, respectively, P<0.0001). These data suggest that gamma-RT and PDT may inhibit restenosis but by different mechanisms. The ef fects of PDT are more diverse and may result in improved outcome while avoi ding the teratogenic exposure due to ionizing irradiation.