gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Monocyte-expressed urokinase inhibits vascular smooth muscle cell growth by activating Stat1

Monozytäre Urokinase inhibiert das Wachstum von VSCM durch die Aktivierung von Stat 1

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker I. Dumler
  • A. Kusch
  • N. Tkatchuk
  • S. Kunigal
  • S. Tkachuk
  • U. Jerke
  • H. Haller

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV36

The electronic version of this article is the complete one and can be found online at:

Published: November 11, 2004

© 2004 Dumler et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



After vascular injury, a remodeling process occurs that features leukocyte migration and infiltration. Loss of endothelial integrity allows the leukocytes to interact with vascular smooth muscle cells (VSMC) and to elicit "marching orders"; however, the signaling processes are poorly understood. Several studies suggest that VSMC migration precedes proliferation and that the uPA/uPAR signaling system may be involved. We asked whether or not VSMC migration is associated with feedback inhibition of cell proliferation and whether this balance might be controlled by underlying signaling pathways. Using a coculture model, we demonstrate that human monocytes inhibit VSMC proliferation and induce a migratory potential.

We provided several lines of evidence that inhibition of VSMC growth is mediated by the transcription factor Stat1 that was activated by the monocyte-expressed uPA and required VSMC-expressed uPAR. We observed Stat1 activation in cocultured VSMC at the level of its Ser727 phosphorylation, nuclear translocation, and DNA binding. This activation was uPA/uPAR-directed and might be abrogated by specific antibodies. We found neither Stat1 activation nor inhibition of VSMC growth in coculture settings where uPA-/- monocytes or uPAR-/- VSMC were used. Our experiments using Stat1-/- VSMC provide direct evidence that this transcription factor was responsible for the growth inhibition observed in coculture. This conclusion was further confirmed in experimental settings where human VSMC with downregulated Stat1 expression (Stat1si-VSMC) were used. Stat1 inactivation by microinjected specific anti-Stat1-pSer727 antibody also resulted in restoration of VSMC proliferation. Our study may explain the increased VSMC migratory potential and the absence of VSMC proliferation observed at the early step of a remodeling process of the vessel wall after vascular injury in humans. Conceivably, a useful strategy for therapeutic intervention could ensue.