201 POSTER Dolichyl phosphate cycle stimulation as a possible mechanism of mdr1 gene suppression in p-388 leukemia cells

Abstract

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<0.01), but did not affect attachment.Conclusions: This report establishes PDT-induced changes in the ECM with a result of inhibition of SMCs and stimulation of EC functions. It provides insight into how PDT-treated arteries can develop favorable EC repopulation without SMC-derived intimal hyperplasia. These findings may help provide a better understanding of the interactions between cells and their immediate environment in vascular remodeling.