Abstract
The studies described herein were undertaken to define the effects of heparin, an angiogenic factor, on endothelial cell (EC) expression of extracellular matrix components. In vitro heparin is known to enhance EC chemotactic and proliferative responses to endothelial cell growth factor (ECGF), a member of the fibroblast growth factor family of mitogens (1, 2). While numerous studies have demonstrated the importance of matrix composition in the regulation of EC attachment (3), migration (4), proliferation (5), and multicellular organization (6), little is known about the effects of angiogenic factors on EC biosynthesis of matrix molecules. In culture, EC synthesize a matrix which contains proteoglycans (7), collagens (8) and other glycoproteins including fibronectin (FN) (9), laminin (10), thrombospondin (11), and plasminogen activator inhibitor-1 (PAI-1) (12). In addition, EC synthesize fibroblast growth factor which they sequester in their matrix (13). In this report, we present data which demonstrate that heparin, in the presence of ECGF, coordinately suppresses EC steady-state mRNA levels for FN, TSP and PAI-1. The suppression of these messages correlates with the potentiation of EC proliferative response to ECGF by heparin. These data suggest a potential role for heparin in the remodeling of extracellular matrix concomitant with neovascularization and further highlight the potential role of matrix components in the autocrine regulation of cell growth.
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Lyons-Giordano, B., Brinker, J.M., Kefalides, N.A. (1992). Heparin Coordinately Suppresses Endothelial Cell Plasminogen Activator Inhibitor-1, Fibronectin and Thrombospondin mRNA Levels. In: Maragoudakis, M.E., Gullino, P., Lelkes, P.I. (eds) Angiogenesis in Health and Disease. NATO ASI Series, vol 227. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3358-0_11
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DOI: https://doi.org/10.1007/978-1-4615-3358-0_11
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