Abstract
Subendothelial invasion and subsequent proliferation of smooth muscle cells (SMCs) are considered to be basic determinants of plaque formation. Inhibitory effects on both cellular events may promise prevention of arteriosclerosis. Calcium antagonists from different groups were screened in a cell culture model with human SMCs cultured from coronary and peripheral lesions on their potential anti-arteriosclerotic properties. SMC proliferative activity was characterized by population doubling rate (PDR), SMC migratory activity was examined by a standardized video-analysis system and quantitated by SMC migratory velocity (V). The calcium channel blockers diltiazem and verapamil (10-7M) did not show effects on PDR and V, whereas isradipine, nicardipine and nifedipine (10-7 M) exerted a significant reduction of these SMC activity parameters. Our data reveal that especially the so-called vasoselective drugs of the dihydropyridine group induce a concordant suppression of cultured plaque SMC proliferative and migratory activities. In vitro studies with SMCs harvested from fresh human plaque tissue were used for a pre-clinical drug screening which may allow a more differential pharmacotherapy of arteriosclerosis.
Zusammenfassung
Subendotheliale Einwanderung und konsekutive Proliferation glatter Muskelzellen (SMCs) sind wesentliche Determinanten der Plaquebildung. Ein inhibitorischer Effekt auf beide zellulären Ereignisse könnte antiarteriosklerotische Wirksamkeit bedeuten. In einem Zellkulturmodell wurden Kalziumantagonisten unterschiedlicher Gruppen auf ihre Eignung als antiarteriosklerotische Substanz an humanen SMCs aus koronaren und femoralen Läsionen getestet. Die SMCProliferationsaktivität wurde durch die Populationsverdoppelungsrate (PDR) charakterisiert, die SMC-Migrationsaktivität wurde mit einem standardisierten Videoanalysesystem gemessen und durch die mittlere Migrationsgeschwindigkeit (V) quantifiziert. Die Kalziumantagonisten Diltiazem und Verapamil blieben bei Konzentrationen von 10-’ M ohne Effekt auf PDR und V, während Isradipin, Nicardipin und Nifedipin in äquimolarer Konzentration eine signifikante Abnahme dieser SMC-Aktivitätsparameter bewirkten. Unsere Untersuchungen zeigen, daß insbesondere die als vasoselektiv geltenden Dihydropyridinderivate konkordant Proliferations- und Migrationsaktivität kultivierter SMCs vermindern. In-vitro-Studien mit glatten Muskelzellen aus humanem Plaquegewebe könnten im Rahmen eines präklinischen Screenings für eine differenziertere Pharmakotherapie der Arteriosklerose bedeutsam sein.
Supported by the Deutsche Forschungsgemeinschaft DFG Ba 1076/1-1
Unterstützt durch Deutsche Forschungsgemeinschaft DFG Ba 1076/1-1
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© 1993 Springer Fachmedien Wiesbaden
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Bauriedel, G., Heimerl, J., Höfling, B., Brandl, R. (1993). Reduction of human plaque smooth muscle cell proliferative and migratory activities by calcium antagonists. In: Heinle, H., Schulte, H., Schaefer, H.E. (eds) Diätetik und Arteriosklerose. Vieweg+Teubner Verlag, Wiesbaden. https://doi.org/10.1007/978-3-663-01942-8_52
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