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Related Experiment Videos

Plasmin induces smooth muscle cell proliferation.

Suzanne M Nicholl1, Elisa Roztocil, Irfan I Galaria

  • 1Division of Vascular Surgery, Department of Surgery, Center for Cardiovascular Research, University of Rochester, Rochester, New York 14642, USA.

The Journal of Surgical Research
|May 5, 2005
PubMed
Summary

Plasmin, generated during thrombolysis, triggers smooth muscle cell proliferation by activating ERK1/2 and PI3-K pathways. Understanding these signaling mechanisms is crucial for preventing intimal hyperplasia post-thrombolysis.

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Area of Science:

  • Vascular Biology
  • Cell Signaling
  • Molecular Medicine

Background:

  • Plasminogen activators are used in thrombolysis, generating plasmin.
  • Plasmin can promote smooth muscle cell proliferation and intimal hyperplasia.
  • The specific signaling pathways activated by plasmin remain unclear.

Purpose of the Study:

  • To elucidate the signaling pathways by which plasmin induces smooth muscle cell proliferation.
  • To investigate the roles of various kinases and G proteins in plasmin-mediated cellular responses.

Main Methods:

  • Murine aortic smooth muscle cells were cultured in vitro.
  • Assays measured DNA synthesis, proliferation, and MAP kinase activation.
  • Cells were treated with plasmin and inhibitors of proteolysis, G proteins (PTx, GP-2A), PI3-K (Wn, LY), MEK (PD), and p38MAPK (SB).

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Main Results:

  • Plasmin stimulated smooth muscle cell DNA synthesis and proliferation, inducing ERK1/2 and p38MAPK phosphorylation.
  • ERK1/2 inhibition blocked proliferation, while p38MAPK inhibition did not.
  • Plasmin-induced ERK1/2 activation involved both Gαi/PI3-K-dependent and Gαq-mediated pathways.

Conclusions:

  • Plasmin directly induces smooth muscle cell proliferation.
  • ERK1/2 phosphorylation is a key mediator, activated via distinct Gαi/PI3-K-dependent and Gαq-independent routes.
  • p38MAPK is not involved in plasmin-induced smooth muscle cell proliferation, differentiating it from other plasminogen activators.