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.

Adili F, Statius van Eps RG, Karp SJ, Watkins MT, LaMuraglia GM
J Vasc Surg. 1996 23 (4): 698-705

PMID: 8627908 · DOI:10.1016/s0741-5214(96)80052-8

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 understood. 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 of ECM significantly enhanced EC proliferation (129% +/- 6.2% vs 100% +/- 6.2%; p < 0.03) and migration (118% +/- 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.

MeSH Terms (20)

Aluminum Animals Aorta Cattle Cell Adhesion Cell Division Cell Movement Cells, Cultured Endothelium, Vascular Extracellular Matrix Free Radicals Hyperplasia Indoles Lasers Muscle, Smooth, Vascular Organometallic Compounds Photochemotherapy Photosensitizing Agents Tunica Intima Tunica Media

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