Molecular Crosstalk Between Adhesion Receptors and Proteolytic Cascades in Vascular Remodelling
| Autor: | M Germer, Andreas E. May, S.M. Kanse, Klaus T. Preissner, Karl-Dieter Wohn |
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| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | Thrombosis and Haemostasis. 78:088-095 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | The multifunctionality of adhesion receptor ligands as well as the promiscuous nature of vascular integrins and nonintegrin-dependent adhesive interactions allow ligand-receptor binding of variable strength. The cooperation with pericellular proteolysis cascades is required for vascular remodelling during angiogenesis, atherogenesis or inflammatory processes. In particular, integrin-dependent cell contact, spreading and (trans-)migration can be modulated by ECM-associated PAI-1 and uPA-receptor driven reactions that are intimately linked to the invasive potential of cells. Recently, mechanisms of molecular crosstalk between these receptor systems have been recognized: (a) uPA-receptor may directly interact with beta 1- and beta 2-integrins on circulating blood cells; (b) av beta 3-integrin-directly binds to a matrix metalloproteinase; (c) uPA and PAI-1 balance the high affinity binding of vitronectin to uPA-receptor; (d) vitronectin-dependent cell adhesion and migration involving alpha v-integrins or uPA-receptor are blocked by active PAI-1 independent of its role as protease inhibitor. These results are compatible with vascular injury studies in uPA- and PAI-1 knock-out mice and provide new targets for the treatment of diseases associated with imbalanced vascular remodelling. |
| Databáze: | OpenAIRE |
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