Angiotensin-converting enzyme inhibition suppresses plasminogen activator inhibitor-1 expression in the neointima of balloon-injured rat aorta.

Abstract

BACKGROUND:

Plasminogen activator inhibitor-1 (PAI-1), an important regulator of fibrinolysis and extracellular matrix turnover, has been implicated in a number of vascular diseases. Studies demonstrating angiotensin II (Ang II) to be a potent stimulator of PAI-1 expression in cultured vascular cells suggests that the renin-angiotensin system may modulate vascular PAI-1 expression.

METHODS AND RESULTS:

We examined the effects of the ACE inhibitor captopril on PAI-1 expression in control and balloon-injured rat aorta. Northern blot analysis demonstrated that aortic PAI-1 mRNA expression was 7.6-fold elevated 3 hours (P<.05) after balloon injury, back to baseline at 2 days, increased again at 4 days, and by 7 days after balloon injury was 3.2-fold elevated (P<.05) when compared with control. In captopril-treated rats, the induction of PAI-1 expression by balloon injury was significantly suppressed by 44% (P<.05) in the 7 day group but was not altered in the 3-hour group. Captopril also reduced baseline aortic PAI-1 mRNA. In situ hybridization and immunohistochemistry revealed dense PAI-1 staining of 7-day neointima in untreated rats and a dramatic decrease in PAI-1 in neointima of captopril-treated rats.

CONCLUSIONS:

This report demonstrates that balloon injury results in both a rapid ACE inhibitor-independent induction of aortic PAI-1 expression and a later increase in PAI-1 in the neointima that is significantly suppressed by captopril. This provides the first evidence that the renin-angiotensin system regulates neointimal PAI-1 expression and that ACE inhibitors can reduce PAI-1 in the vessel wall in vivo.

• Authors: A D Hamdan, W C Quist, J B Gagne, E P Feener
• Journal: Circulation (Circulation) Vol. 93 Issue 6 Pg. 1073-8 (Mar 15 1996) ISSN: 0009-7322 [Print] United States
• PMID: 8653825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Plasminogen Activator Inhibitor 1
• RNA, Messenger
• Captopril

Topics

• Angioplasty, Balloon
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Aorta (metabolism)
• Captopril (pharmacology)
• Immunohistochemistry
• In Situ Hybridization
• Male
• Muscle, Smooth, Vascular (metabolism)
• Plasminogen Activator Inhibitor 1 (analysis, biosynthesis, genetics)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley