Photodynamic therapy with motexafin lutetium induces redox-sensitive apoptosis of vascular cells

Citation
Zp. Chen et al., Photodynamic therapy with motexafin lutetium induces redox-sensitive apoptosis of vascular cells, ART THROM V, 21(5), 2001, pp. 759-764
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
21
Issue
5
Year of publication
2001
Pages
759 - 764
Database
ISI
SICI code
1079-5642(200105)21:5<759:PTWMLI>2.0.ZU;2-H
Abstract
Motexafin lutetium is a photosensitizer that accumulates in atherosclerotic plaque and, after activation by far-red Light, produces cytotoxic singlet oxygen. The combination of photosensitizer and illumination, known as photo dynamic therapy (PDT), has been shown to reduce atheroma formation in anima l models and is under clinical investigation. However, the effects of PDT w ith motexafin lutetium on isolated vascular cells are unknown. This study w as designed to characterize the effects of PDT on vascular cell viability a nd to define the cell-death pathway for this agent. Fluorescence microscopy of RAW macrophages and human vascular smooth muscle cells revealed time-de pendent uptake of motexafin lutetium, Illumination of motexafin lutetium-lo aded cells with 732-nm light (2 J/cm(2)) impaired cellular viability and gr owth (IC50 5 to 20 mu mol/L). Depletion of intracellular glutathione potent iated (P=0.035) and the addition of antioxidant N-acetylcysteine attenuated (P=0.002) cell death, suggesting that the intracellular redox state influe nces motexafin lutetium action. PDT was associated with the loss of mitocho ndrial membrane potential, mitochondrial release of cytochrome c, and caspa se activation. PDT promoted phosphatidylserine externalization and induced apoptotic DNA fragmentation, with the number of apoptotic cells increasing from 7+/-2% to 34+/-3% of total cells. Reducing plaque cellularity by the i nduction of apoptosis may be one mechanism by which PDT reduces plaque burd en, possibly modulates plaque vulnerability, and inhibits restenosis in viv o.