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American Journal of Pathology, Vol 134, 497-503, Copyright © 1989 by American Society for Investigative Pathology

REGULAR ARTICLES

Endothelial stimulation of intimal cell proliferation in a porcine aortic organ culture

EW Koo and AI Gotlieb
Department of Pathology, Banting and Best Diabetes Centre, University of Toronto, Toronto General Hospital, Ontario, Canada.

A porcine thoracic aortic organ culture system was used to study the interaction between endothelial cells (EC) and the underlying intimal smooth muscle cells (SMC). The presence of EC in organ cultures was confirmed by the ability of luminal cells to incorporate acetylated- LDL. It was found that incubation of nondenuded organ cultures in 5% fetal bovine serum for 7 days resulted in a significant increase in the mean number of intimal SMC (41.5 +/- 0.9) compared with organ cultures in which the endothelium was removed at the beginning of the experiment (denuded, 15.2 +/- 0.8). Incubation of the latter for 7 days in conditioned medium collected from nondenuded organ cultures also resulted in a significant increase in the mean number of intimal SMC (30.2 +/- 2.2). Incubation of aortic medial SMC cultures in the conditioned medium also enhanced SMC growth. Autoradiography studies at each day of the 7 days showed that intimal SMC proliferation was similar in both nondenuded and denuded organ cultures when the latter was incubated in the conditioned medium. These data suggests that in this model the secretion of a soluble mediator by dysfunctioning, injured, or proliferating endothelial cells stimulates intimal cell proliferation either directly or indirectly.

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