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Endothelial Injury Induces Vascular Smooth Muscle Cell Proliferation in Highly Localized Regions of a Direct Contact Co-culture System

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Abstract

Though previous studies have indicated a relationship between the proliferation of endothelial cells and vascular smooth muscle cells (VSMCs) in co-culture, the results have been contradictory and the signaling mechanism poorly understood. In this transmembrane co-culture study, VSMCs and endothelial cells were grown to confluence on opposite sides of a microporous membrane to mimic the intima/media border of vessels. The endothelial layer was injured, and then cultured for 3 days, resulting in partial re-endothelialization. VSMC proliferation across from the injured/partially recovered endothelial region was significantly higher than across from the de-endothelialized region (a sevenfold increase) and the uninjured region (a threefold increase). ELISA indicated that PDGF, which was undetectable in uninjured co-culture and homotypic controls, increased after injury and the addition of a piperazinyl-quinazoline carboxamide PDGF receptor inhibitor blocked VSMC proliferation across from the injured/partially recovered region. We conclude that co-culture signaling initiated by endothelial cell injury locally stimulates VSMC proliferation and that this signaling could be mediated by PDGF-BB.

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Acknowledgments

We thank P. Cook and M. Nugent for helpful discussions, E. Bartolak-Suki for critical reading of the manuscript, and C. Piron and E. Cosgrove for technical assistance with image analysis. This work was supported by the National Institute of Health (R01 HL72900-01), NASA (NAG9-1558) and a National Science Foundation CAREER Award (BES-9985338) to J.Y.W.

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  1. Department of Biomedical Engineering, Boston University, 44 Cummington St, Boston, MA, 02215, USA

    Jeffrey G. Jacot & Joyce Y. Wong

  2. Rice University, 6100 Main St. MS-142, Houston, TX, 77005, USA

    Jeffrey G. Jacot

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Correspondence to Jeffrey G. Jacot or Joyce Y. Wong.

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Jacot, J.G., Wong, J.Y. Endothelial Injury Induces Vascular Smooth Muscle Cell Proliferation in Highly Localized Regions of a Direct Contact Co-culture System. Cell Biochem Biophys 52, 37–46 (2008). https://doi.org/10.1007/s12013-008-9023-6

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