Abstract 10495: PAI-1 Has a Significant Role in Arterial Remodeling after Mechanical Injury in Mice
Background: Plasminogen activator inhibitor-1 (PAI-1) is critical in thrombus formation and inflammation. Many studies indicate that PAI-1 also plays a pivotal role in vascular remodeling. However, the role of PAI-1 on neointimal hyperplasia after arterial injury is controversial. Using an IKK inhibitor IMD-0354 and PAI-1(-/-) mice, we examined effects of PAI-1 on neointimal hyperplasia.
Hypothesis: We assessed the hypothesis that PAI-1 inhibition prevented neointimal hyperplasia after wire-mediated arterial injury.
Method: Using wild-type and PAI-1(-/-) C57BL/6J mice, we made a wire-injury model. We intraperitoneally injected IMD-0354 twice a day. The arteries were harvested for pathological and molecular analysis on days 7 and 28 after injury.
Results: Wild-type injured arteries showed significantly thickened intima (3.77±0.59, n=8), which was suppressed in PAI-1(-/-) arteries (2.19±0.34, n=13, p<0.05) on day 28. Immunohistochemistry revealed that there was no significant difference between arteries of wild-type and PAI-1(-/-) mice in CD4, 8 and 11b positive cell infiltration. Quantitative RT-PCR showed that PAI-1 mRNA expression was comparable in IMD-0354 treated (0.12±0.02, n=7) and non-treated arteries (0.20±0.04, n=10) on day 28. Western blotting revealed that PAI-1 protein expression was enhanced in the vehicle group on day 7 (77.6±3.9, n=5), while IMD-0354 treatment significantly reduced expression (50.2±8.1, n=6, p<0.05).
Conclusion: PAI-1 knockout inhibited neointimal hyperplasia after wire-mediated arterial injury, and the IKK inhibition down-regulated PAI-1 production in this model. In conclusion, PAI-1 is an essential factor in the progression of vascular remodeling and its inhibition can prevent restenosis after arterial injury.
- © 2011 by American Heart Association, Inc.