Photochemotherapy of vascular cells with 8-methoxypsoralen and visible light: differential effects on endothelial and smooth muscle cells.
BACKGROUND
The long-term efficacy of percutaneous transluminal coronary angioplasty is limited by the restenosis which occurs in approximately 40% of patients, usually within 6 months of the procedure.


OBJECTIVE
The present study was designed to evaluate the effects of 8-methoxypsoralen (8-MOP) activated with visible light on the properties of bovine aortic smooth muscle cells (SMC) and endothelial cells (EC) in vitro.


METHODS
Cells were seeded in polystyrene wells, allowed to attach over a 24-h period, incubated with 1, 20, or 50 microg/ml 8-MOP and then exposed to 12 J/cm2 visible light (447 nm). Cell counts were performed for up 14 days (n = 4-6 wells per time point), and each experiment was performed in triplicate. Cellular migration, morphology, and size were also analyzed.


RESULTS
The lowest 8-MOP dose (1 microg/ml) had no significant effect on SMC proliferation, while the highest dose (50 microg/ml) induced cytostasis. An intermediate dose of 8-MOP (20 microg/ml) produced a transient and reversible inhibition of proliferation. There was no significant effect on proliferation of EC at lowest dose of 8-MOP (1 microg/ml). However, in contrast to the SMC experiments, a transient and reversible inhibition of EC proliferation was seen at both 20 and 50 microg/ml 8-MOP.


CONCLUSIONS
These experiments demonstrate that while 8-MOP photoactivated with 447 nm visible light can reversibly inhibit the proliferation of both SMC and EC in a dose-dependent fashion, SMC are more sensitive to the treatment than EC.
Lee
David M
DM
Department of Surgery (Vascular), Yale University School of Medicine, New Haven, CT 06510, USA.
Gasparro
Francis P
FP
Wang
Xiu Jie
XJ
Kopec
Chris
C
DeLeo
Kier
K
Sumpio
Bauer E
BE
D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D008730:Methoxsalen / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D010778:Photochemotherapy / Q000379:methods*
D008730:Methoxsalen