Photodynamic therapy generates a matrix barrier to invasive vascular cell migration

Photodynamic therapy (PDT) inhibits experimental intimal hyperplasia, PDT r esults in complete vascular wall cell eradication with subsequent adventiti a but minimal media repopulation. This study was designed to rest the hypot hesis that PDT alters the vascular wall matrix thereby inhibiting invasive cell migration, and :Is such, provides an important barrier mechanism to fa vorably alter the vascular injury response. Untreated smooth muscle cells ( SMCs) and fibroblasts were seeded on control and PDT-treated (100 J/cm(2); photosensitizer was chloroaluminum-sulfonated phthalocyanine, 5 mu g/mL) 3- dimensional collagen matrix gels. Invasive cell migration was temporally qu antified by calibrated microscopy, Zymography and ELISA assessed SMC matrix metalloproteinase levels. Molecular changes of gel proteins and their susc eptibility to collagenase were analyzed by SDS-PAGE and Western blot. Limit ed pepsin digestion and histology were used to assess the in vivo relevance of the model, using an established rat carotid artery model at 1 and 4 wee ks after balloon injury and PDT. PDT of 3-dimensional matrix of gels led to a 52% reduction of invasive SMCs and to a 59% reduction of fibroblast migr ation (P<0.001) but did not significantly affect secretion of matrix metall oproteinases. PDT induced collagen matrix changes, including cross-linking, which resulted in resistance to protease digestion. PDT led to a durable 4 5% reduction in pepsin digestion susceptibility of treated arteries (P<0.00 1) and inhibition of periadventitial cell migration into the media. These d ata suggest that PDT of matrix gels generates a barrier to invasive cellula r migration. This newly identified effect on matrix proteins underscores it s pleiotropic actions on the vessel wall, and as such, PDT may be of consid erable potential therapeutic value to inhibit restenosis.