In vitro photodynamic therapy with chlorin e6 leads to apoptosis of human vascular smooth muscle cells.
Percutaneous coronary intervention has become the most common and widely implemented method of heart revascularization. However, the development of restenosis remains the major limitation of this method. Photodynamic therapy (PDT) recently emerged as a new and promising method for the prevention of arterial restenosis. Here the efficacy of chlorin e6 in PDT was investigated in vitro using human vascular smooth muscle cells (TG/HA-VSMCs) as one of the cell types crucial in the development of restenosis. PDT-induced cell death was studied on many levels,including annexin V staining, measurement of the generation reactive oxygen species (ROS) and caspase-3 activity,and assessment of changes in mitochondrial membrane potential and fragmentation of DNA. Photosensitization of TG/HA-VSMCs with a 170 lM of chlorin e6 and subsequent illumination with the light of a 672-nm diode laser(2 J/cm2) resulted in the generation of ROS, a decrease in cell membrane polarization, caspase-3 activation, as well as DNA fragmentation. Interestingly, the latter two apoptotic events could not be observed in photosensitized and illuminated NIH3T3 fibroblasts, suggesting different outcomes of the model of PDT in various types of cells. The results obtained with human VSMCs show that chlorin e6 may be useful in the PDT of aerial restenosis, but its efficacy still needs to be established in an animal model.
Wawrzyńska
Magdalena
M
Department of Cardiology, Wrocław Medical University, Wroclaw, Poland.
Kałas
Wojciech
W
Biały
Dariusz
D
Zioło
Ewa
E
Arkowski
Jacek
J
Mazurek
Walentyna
W
Strzadała
Leon
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism; D002735:Chlorophyllides; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D006801:Humans; D007834:Lasers; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000528:radiation effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D041681:NIH 3T3 Cells; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*; D017382:Reactive Oxygen Species
D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C062985:phytochlorin; D053148:Caspase 3