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A novel in vitro model for the study of plaque development in atherosclerosis.
Thromb Haemost. 2006 Jan; 95(1):182-9.TH

Abstract

For the study of atherogenesis in vitro, coculture systems have been devised, in which two or more cell types can be cultured in close contact to each other. Herein, we describe a novel in vitro model that aims at the simulation of the morphology of a normal muscular artery allowing for the study of the initial events in atherosclerosis. Using a modified fibrin gel as a scaffold for the coculture of endothelial cells (ECs) and smooth muscle cells (SMCs), we generated an autologous in vitro model with a multilayer growth of SMCs (intima-like structure) covered by an endothelium. The production of extracellular matrix (ECM) could be visualized histologically and verified by (i) ascorbic-acid dependent secretion of procollagen I into the supernatant and (ii) deposition of collagens I and III as well as laminin in the gel as assessed by immunohistochemistry. By BrdU-incorporation and Ki67 expression, the SMCs exhibited minimal proliferative activity, even when the culture period was extended to 6 weeks. Lipoprotein insudation was investigated under simulated hypo-, normo- and hypercholesterolemic conditions through addition of 0.5, 1 or 2 mg/mL LDL to the medium with subsequent time and dose dependent insudation of LDL. When human monocytes were added to the culture medium, infiltration and foam cell formation of macrophages and SMCs as well as expression of interleukin-8 (IL-8) was demonstrated. The in vitro model of the human vascular wall described herein appears to be suitable for the study of pivotal events in atherosclerotic plaque development. The applicability for long-term culture, the ability to study cell-matrix interactions and the opportunities for histomorphological and immunohistochemical examinations represent additional advantages of this model.

Authors+Show Affiliations

Department of Cardiothoracic and Vascular Surgery, University of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. dorweiler@htg.klinik.uni-mainz.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16543978

Citation

Dorweiler, Bernhard, et al. "A Novel in Vitro Model for the Study of Plaque Development in Atherosclerosis." Thrombosis and Haemostasis, vol. 95, no. 1, 2006, pp. 182-9.
Dorweiler B, Torzewski M, Dahm M, et al. A novel in vitro model for the study of plaque development in atherosclerosis. Thromb Haemost. 2006;95(1):182-9.
Dorweiler, B., Torzewski, M., Dahm, M., Ochsenhirt, V., Lehr, H. A., Lackner, K. J., & Vahl, C. F. (2006). A novel in vitro model for the study of plaque development in atherosclerosis. Thrombosis and Haemostasis, 95(1), 182-9.
Dorweiler B, et al. A Novel in Vitro Model for the Study of Plaque Development in Atherosclerosis. Thromb Haemost. 2006;95(1):182-9. PubMed PMID: 16543978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel in vitro model for the study of plaque development in atherosclerosis. AU - Dorweiler,Bernhard, AU - Torzewski,Michael, AU - Dahm,Manfred, AU - Ochsenhirt,Viola, AU - Lehr,Hans-Anton, AU - Lackner,Karl J, AU - Vahl,Christian-Friedrich, PY - 2006/3/18/pubmed PY - 2006/4/28/medline PY - 2006/3/18/entrez SP - 182 EP - 9 JF - Thrombosis and haemostasis JO - Thromb Haemost VL - 95 IS - 1 N2 - For the study of atherogenesis in vitro, coculture systems have been devised, in which two or more cell types can be cultured in close contact to each other. Herein, we describe a novel in vitro model that aims at the simulation of the morphology of a normal muscular artery allowing for the study of the initial events in atherosclerosis. Using a modified fibrin gel as a scaffold for the coculture of endothelial cells (ECs) and smooth muscle cells (SMCs), we generated an autologous in vitro model with a multilayer growth of SMCs (intima-like structure) covered by an endothelium. The production of extracellular matrix (ECM) could be visualized histologically and verified by (i) ascorbic-acid dependent secretion of procollagen I into the supernatant and (ii) deposition of collagens I and III as well as laminin in the gel as assessed by immunohistochemistry. By BrdU-incorporation and Ki67 expression, the SMCs exhibited minimal proliferative activity, even when the culture period was extended to 6 weeks. Lipoprotein insudation was investigated under simulated hypo-, normo- and hypercholesterolemic conditions through addition of 0.5, 1 or 2 mg/mL LDL to the medium with subsequent time and dose dependent insudation of LDL. When human monocytes were added to the culture medium, infiltration and foam cell formation of macrophages and SMCs as well as expression of interleukin-8 (IL-8) was demonstrated. The in vitro model of the human vascular wall described herein appears to be suitable for the study of pivotal events in atherosclerotic plaque development. The applicability for long-term culture, the ability to study cell-matrix interactions and the opportunities for histomorphological and immunohistochemical examinations represent additional advantages of this model. SN - 0340-6245 UR - https://www.unboundmedicine.com/medline/citation/16543978/A_novel_in_vitro_model_for_the_study_of_plaque_development_in_atherosclerosis_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=16543978.ui DB - PRIME DP - Unbound Medicine ER -