Endothelial cells inhibit flow-induced smooth muscle cell migration: Role of plasminogen activator inhibitor-1

Eileen M. Redmond*, John P. Cullen, Paul A. Cahill, James V. Sitzmann, Steingrimur Stefansson, Daniel A. Lawrence, S. Steve Okada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)


Background - The endothelium may play a pivotal role in hemodynamic force-induced vascular remodeling. We investigated the role of endothelial cell (EC) plasminogen activator inhibitor-1 (PAI-1) in modulating flow-induced smooth muscle cell (SMC) migration. Methods and Results - Human SMCs cocultured with or without human ECs were exposed to static (0 mL/min) or flow (26 mL/min; shear stress 23 dyne/cm2) conditions for 24 hours in a perfused capillary culture system. SMC migration was then assessed with a Transwell migration assay. In the absence but not in the presence of ECs, pulsatile flow significantly increased the migration of SMCs (264±26%) compared with SMCs under static conditions, concomitant with a 3- and 4-fold increase in PAI-1 mRNA and protein, respectively, in cocultured ECs. In the presence of PAI-1 -/ECs, flow increased wild-type SMC migration (226±25%), an effect that was reversed by exogenous PAI-1. To determine whether the antimigratory activity of PAI-1 was dependent primarily on inhibition of PAs or its association with vitronectin, experiments were conducted with PAI-1R (a mutant PAI-1 that binds to vitronectin but does not inhibit PA) and PAI-1K (a mutant that inhibits PA but has reduced affinity for vitronectin). PAI-1R inhibited both basal and flow-induced migration, whereas PAI-1K inhibited flow-induced migration in the absence of any effect on baseline migration. Conclusions - Flow-induced EC PAI-1 inhibits flow-induced SMC migration in vitro. EC PAI-1 expression may be one of the predominant mechanisms responsible for controlling the process of vascular remodeling.

Original languageEnglish
Pages (from-to)597-603
Number of pages7
Issue number4
Publication statusPublished - 30 Jan 2001

Other keywords

  • Atherosclerosis
  • Endothelium
  • Muscle, smooth
  • Plasminogen activators
  • Stress


Dive into the research topics of 'Endothelial cells inhibit flow-induced smooth muscle cell migration: Role of plasminogen activator inhibitor-1'. Together they form a unique fingerprint.

Cite this