(Circulation. 1996;93:1073-1078.)
© 1996 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme Inhibition Suppresses Plasminogen Activator Inhibitor-1 Expression in the Neointima of Balloon-Injured Rat Aorta
From the Research Division of the Joslin Diabetes Center (J.B.G., A.D.H., E.P.F.) and the Departments of Vascular Surgery (A.D.H., W.C.Q.) and Pathology (W.C.Q.), Deaconess Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Edward P. Feener, PhD, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail FEENERE@Joslab.Harvard.EDU.
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.
Key Words: plasminogen • angiotensin • aorta • balloon • catheterization
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