[Effect of dihematoporphyrin derivatives on cultivated human smooth muscle cells from normal and atherosclerotic vascular segments-- Overview of results and implications for photodynamic therapy].
It is little known that photosensitizing porphyrins can be used not only for the localization and photodynamic therapy of tumors, but that they also accumulate in atherosclerotic plaques. This observation might be of interest for the detection and therapy of vascular stenoses. The present study examines whether dihematoporphyrin-ester and -ether, at clinically relevant concentrations, selectively influence cultured smooth muscle cells from human atherosclerotic plaques (primary stenoses and secondary stenoses) in comparison to smooth muscle cells obtained from non-atherosclerotic arteries. The results demonstrate that the drug accumulated to a greater extent in plaque-derived cells than in smooth muscle cells from normal arteries. Even without photoactivation, dihematoporphyrin-ester and -ether significantly decreased the proliferative activity of cells from atherosclerotic plaques. Light exposure of porphyrin-labeled cells resulted in a more pronounced sensitivity of plaque cells when compared with smooth muscle cells from non-atherosclerotic arterial wall. A comparison of the proliferative activity of cells before and after photodynamic reaction demonstrated that this activity was unaltered in surviving smooth muscle cells from non-atherosclerotic arteries, whereas surviving plaque-derived cells exhibited a significantly decreased or even non-proliferative activity. From the in vitro studies, a porphyrin concentration of 1-5 micrograms/ml (= 1-5 mg/kg body weight in vivo after systemic application) seems to be the most suitable dosage. In addition, morphological alterations of the cells caused by photodynamic reaction were documented.(ABSTRACT TRUNCATED AT 250 WORDS)
Dartsch
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Physiologisches Institut I, Universität Tübingen.
Betz
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Ischinger
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D000328:Adult; D001161:Arteriosclerosis / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D017323:Dihematoporphyrin Ether; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005260:Female; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology
D006415:Hematoporphyrins; D017323:Dihematoporphyrin Ether
Wirkung von Dihämatoporphyrin-Derivaten auf kultivierte glatte Muskelzellen des Menschen aus normalen und atherosklerotisch veränderten Gefässsegmenten--Ubersicht über bisherige Ergebnisse und Implikationen für eine photodynamische Therapie.