Photodynamic therapy inhibits the injury-induced fibrotic response of vascular smooth muscle cells.
OBJECTIVE
excessive deposition of extracellular matrix (ECM) proteins plays a key role in the intervention-related vascular fibroproliferative response, resulting in intimal hyperplasia (IH). Cytokines, such as platelet-derived 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 produce free radicals, is a novel approach to inhibit experimental IH by the local eradication of smooth-muscle cells (SMC) and alteration of ECM. This in vitro study examined whether PDT can inhibit the fibrotic response of vascular SMC.


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 [3H]-proline incorporation.


RESULTS
untreated SMC seeded on ECM demonstrated an increase of 50% in collagen production ( p <0.0001) as compared to SMC on an empty plate. This increase was also seen when SMC was incubated with the conditioned media of mechanically injured SMC, or pure PDGF. However, after PDT of ECM, injured SMC or PDGF, there was an inhibition of 40% ( p <0.05) in SMC-collagen production.


CONCLUSIONS
these findings indicate that PDT can interfere with factors that lead to the vascular fibrotic response. In this way, PDT, with its cytotoxic and extracellular effects, can promote healing of the vessel wall without the stimulus of fibrosis that can lead to restenosis.
Statius van Eps
R G
RG
Division of Vascular Surgery of the General Surgical Services, Wellman Laboratories of Photomedicine, Boston, MA 02114, USA.
Mark
L L
LL
Schiereck
J
J
LaMuraglia
G M
GM
D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects / Q000528:radiation effects; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000528:radiation effects; D005355:Fibrosis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D010778:Photochemotherapy / Q000379:methods / Q000706:statistics & numerical data; D010982:Platelet-Derived Growth Factor / Q000187:drug effects / Q000528:radiation effects
D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D010982:Platelet-Derived Growth Factor; D003094:Collagen