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Photochemically Modulated Endothelial Cell Thrombogenicity via the Thrombomodulin–Tissue Factor Pathway ¶
Author(s) -
Fungaloi Patrick,
Waterman Peter,
Nigri Giuseppe,
Statiusvan Eps Randolph,
Sluiter Wim,
Van Urk Hero,
LaMuraglia Glenn
Publication year - 2003
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2003)0780475pmectv2.0.co2
Subject(s) - tissue factor , thrombomodulin , thrombogenicity , photodynamic therapy , flow cytometry , endothelial stem cell , umbilical vein , chemistry , cancer research , photosensitizer , thrombosis , biophysics , coagulation , medicine , thrombin , immunology , in vitro , biology , platelet , biochemistry , photochemistry , organic chemistry
Photodynamic therapy (PDT) is based on a photochemical reaction using a photosensitizer and light to produce reactive oxygen species that have biological effects. Although its application in some fields is largely based on thrombosis, in the vascular setting thrombosis must be prevented. In this study we examined the effects of PDT on the changes in activity of thrombomodulin (TM) and tissue factor (TF) as important regulators of the coagulation process of endothelial cells. Human umbilical vein endothelial cells were treated with PDT (chloro‐aluminum‐sulfonated phthalocyanine, λ= 630 nm) at different light‐energy doses, and TM and TF levels were measured using fluorescence spectroscopy. Microparticles (MP) were analyzed using flow cytometry analysis. PDT alters the thrombogenic state of endothelial cells by causing decreased expression of TM and increased expression of functional TF in a light‐energy dose–dependent way. PDT‐treated endothelial cells shed large numbers of MP containing high levels of TF. TF functionality of PDT‐treated cells, measured by a Factor Xa–generating assay, was high. TF was located mostly intracellularly and in MP. The disturbed anticoagulant balance described in this study may explain the occurrence of thrombosis induced by PDT and, if not contained, dispute the suitability of PDT as an adjuvant modality to treat vascular restenosis.