Photodynamic therapy inactivates extracellular matrix-basic fibroblast growth factor: insights to its effect on the vascular wall.

LaMuraglia GM, Adili F, Karp SJ, Statius van Eps RG, Watkins MT
J Vasc Surg. 1997 26 (2): 294-301

PMID: 9279318 · DOI:10.1016/s0741-5214(97)70192-7

PURPOSE - Photodynamic therapy (PDT), the light activation of photosensitizer dyes for the production of oxygen and other free radical moieties without the generation of heat, has been shown to inhibit the development of experimentally induced intimal hyperplasia. The host response to PDT, a form of vascular injury that results in complete vascular wall cell eradication, is devoid of inflammation and proliferation and promotes favorable vascular wall healing. These effects do not result in intimal hyperplasia and are suggestive of PDT-induced changes in the extracellular matrix (ECM). As a model to better understand the biologic consequences of PDT on the vascular wall matrix proteins, the effect of PDT was studied on the powerful matrix-resident mitogen basic fibroblast factor (bFGF) in vitro.

METHODS - PDT (5 to 200 J/cm2, 100 mW/cm2, 675 nm) was used with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 micrograms/ml) to inactivate bFGF in vitro while 100 J/cm2 of irradiation was administered 24 hours after 5 mg/ml of the photosensitizer was used in vivo. PDT was used on bFGF in solution and on endothelial cell-derived ECM. Enzyme-linked immunosorbent assay was used to quantitate bFGF in solution after PDT treatment or after extraction from the ECM by collagenase and heparin. Functional activity of matrix-associated bFGF was assessed by smooth muscle cell mitogenesis by 3H-thymidine incorporation. To demonstrate the in vivo relevance of these observations, immunohistochemical analysis of PDT-treated rat carotid arteries was undertaken.

RESULTS - PDT eliminated detectable levels of bFGF in solution. PDT of ECM significantly reduced matrix-bound bFGF (1.0 +/- 0.6 vs 27.5 +/- 1.3 pg/ml; p < 0.0001). This reduction in bFGF after PDT of the ECM was associated with a decrease in vascular smooth muscle cell mitogenesis (52.4% +/- 4.6%; p < 0.0001) when plated on PDT-treated matrix compared with nontreated matrix. Quantitative replenishment of exogenous bFGF to PDT-treated matrix restored proliferation to baseline levels. PDT of rat carotid arteries demonstrated a loss of bFGF staining compared with control nontreated arteries.

CONCLUSIONS - PDT inactivation of matrix-resident bFGF and possibly other bioactive molecules can provide a mechanism by which PDT suppresses smooth muscle cell proliferation in the vessel wall. This free radical-mediated alteration of matrix may contribute to favorable vascular healing when PDT is used for the inhibition of injury-induced intimal hyperplasia.

MeSH Terms (12)

Animals Antibodies, Monoclonal Aorta Cattle Cells, Cultured Enzyme-Linked Immunosorbent Assay Extracellular Matrix Fibroblast Growth Factor 2 Muscle, Smooth, Vascular Photochemotherapy Rats Rats, Sprague-Dawley

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