Molecular crosstalk between adhesion receptors and proteolytic cascades in vascular remodelling.
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.
Preissner
K T
KT
Haemostasis Research Unit, Kerchoff-Klinik, Bad Nauheim, Germany. klaus.t.preissnerkerckhoff.med.uni-giessen.de
May
A E
AE
Wohn
K D
KD
Germer
M
M
Kanse
S M
SM
D000818:Animals; D001773:Blood Cells / Q000502:physiology; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D006868:Hydrolysis; D016023:Integrins / Q000378:metabolism*; D051379:Mice
D016326:Extracellular Matrix Proteins; D016023:Integrins; D010450:Endopeptidases