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Pathogenese der Atherosklerose: Evaluation eines Modelles zur In-vitro-Simulation der Plaqueentstehung

Pathogenesis of atherosclerosis: Evaluation of an in vitro model for the simulation of plaque development

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Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Zur Untersuchung der Pathogenese der Atherosklerose wurden verschiedene In-vitro-Zellkultursysteme entwickelt, die zum Teil auf Mono-, zum Teil auf Kokulturmodellen basieren. In der vorliegenden Arbeit beschreiben wir die Entwicklung eines homologen humanen dreidimensionalen Kokulturmodelles das in Form einer Neo-Intima die menschliche Gefäßwand in vitro nachbildet. Durch Kokultur von humanen glatten Muskelzellen und Endothelzellen in einer Fibrinmatrix konnten charakteristische Elemente der Gefäßwand wie mehrschichtiges Wachstum glatter Muskelzellen, konfluenter Endothelzellmonolayer und Sekretion extrazellulärer Matrix nachgebildet werden. Nach Zugabe von humanem Low Density Lipoprotein war eine dosis- und zeitabhängige Insudation des Lipides subendothelial zu verzeichnen und in Zusammenhang mit der Adhäsion, Transmigration und Schaumzellbildung humaner Monozyten, die mit dem LDL-beladenen Modell inkubiert wurden, konnte die potentielle Eignung dieses Modelles zur Simulation der Plaqueentstehung in vitro gezeigt werden.

Abstract

For the study of the pathogenesis of atherosclerosis, different in vitro models have been developed that are based on the monoor coculture of endothelial and smooth muscle cells. Herein, we describe the development of a three-dimensional homologous coculture model that resembles the human neo-intima. Using coculture of human smooth muscle cells and endothelial cells in a fibrin gel matrix, characteristic features of the human vessel wall, e.g., multilayer growth of smooth muscle cells, confluent luminal endothelial monolayer and extracellular matrix production were achieved. Following addition of human low density lipoprotein to the cell culture medium, a dose- and time-dependent subendothelial insudation of the lipid was noted and human monocytic cells when incubated with the model showed adhesion, transmigration and subendothelial foam cell formation. This review updates the current knowledge of the pathogenesis of atherosclerosis, outlines contemporary models for in vitro research and demonstrates the potential applicability of our model for the simulation of plaque development.

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  1. Klinik für Herz-, Thorax- und Gefäßchirurgie, Universitätsklinik Mainz, Langenbeckstraße 1, 55131, Mainz, Germany

    B. Dorweiler & C.-F. Vahl

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Dorweiler, B., Vahl, CF. Pathogenese der Atherosklerose: Evaluation eines Modelles zur In-vitro-Simulation der Plaqueentstehung. Z Herz- Thorax- Gefäßchir 21, 225–235 (2007). https://doi.org/10.1007/s00398-007-0596-y

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