Differential modulation of vascular endothelial and smooth muscle cell function by photodynamic therapy of extracellular matrix: Novel insights into radical-mediated prevention of intimal hyperplasia

Purpose: Photodynamic therapy (PDT) has been demonstrated to inhibit experimental intimal hyperplasia and to lead to expedient reendothelialization but negligible repopulation of the vessel media. The mechanism that underlies the differential ingrowth of cells into PDT-treated vessel segments is not undertood. Because the extracellular matrix (ECM) is known to modulate specific cell functions, this study was designed to determine whether PDT of isolated ECM affects the function of endothelial cells (ECs) and smooth muscle cells (SMCs).Methods: PDT of bovine aortic EC-ECM was performed with chloroaluminum sulfonated phthalocyanine and 675-nm laser light. Control specimens included untreated ECM, ECM-free plates, and ECM exposed to either light or photosensitizer only. Cell function was characterized by attachment, proliferation, and migration of ECs or SMCs that were plated onto identically treated matrixes.Results: SMC attachment (86%±0.4% vs 95%±0.4%), proliferation (46%±0.5% vs 100%±1.4%), and migration (40%±1.0% vs 100%±0.9%) were significantly inhibited after PDT of ECM when compared with untreated ECM (all p<0.001). In contrast, PDT and migration (118%±1.2% vs 100%±0.8; p