Photodynamic therapy inhibits the injury-induced fibrotic response of vascular smooth muscle cells

Objectives: excessive deposition of extracellular matrix (ECM) proteins pla ys a key role in the intervention-related vascular fibroproliferative respo nse, resulting in intimal hyperplasia (IH). Cytokines, such as Platelet-der ived growth factor (PDGF), released after vascular injury and deposited in the ECM, are known to stimulate production of matrix proteins. Photodynamic therapy (PDT), the combination of light and a photosensitive dye to produc e free radicals, is a novel approach to inhibit experimental IH by the loca l eradication of smooth-muscle cells (SMC) and alteration of ECM. This in v itro study examined whether PDT can inhibit the fibrotic response of vascul ar SMC. Materials and methods: the Effect of PDT on important pro-fibrotic factors was determined by performing PDT of isolated ECM, injured SMC and pure PDGF . SMC production of collagen was monitored by cellular [H-3]-proline incorp oration. Results: untreated SMC seeded on ECM demonstrated an increase of 50% in col lagen production (p<0.0001) as compared to SMC on an empty plate. This incr ease was also seen when SMC tons incubated with the conditioned media of me chanically injured SMC, or pure PDGF. However, after PDT of ECM, injured SM C or PDGF, there was an inhibition of 40% (p<0.05) in SMC-collagen producti on. Conclusions: these findings indicate that PDT can interfere with factors th at lead to the vascular fibrotic response. In this way, PDT, with its cytot oxic and extracellular effects, can promote healing of the vessel wall with out the stimulus of fibrosis that can lend to restenosis.