Deleterious effects of lack of cardiac PAI-1 after coronary occlusion in mice and their pathophysiologic determinants.
We sought to delineate mechanisms through which the lack of plasminogen activator inhibitor (PAI)-1 in the heart affects remodeling of the heart early after myocardial infarction (MI). MI was induced by coronary occlusion in 10-weeks old PAI-1 knockout (KO) and control mice. Three days after MI, systolic and diastolic function was assessed with high-resolution echocardiography, infarct size was determined biochemically and histologically and accumulation of acute inflammatory cells in zones of infarction was characterized by immunocytochemistry. PAI-1 KO mice exhibited markedly thickened diastolic left ventricular anterior walls (1.38 +/- 0.38 mm vs. 0.77 +/- 0.13 SD), more profound depression of global and regional cardiac function (19 vs. 22% fractional shortening), and greater evidence of diastolic dysfunction (average E wave amplitude = 568 vs. 675 mm/s) all of which were significant. Markedly greater extent of infarction was demonstrated biochemically and histologically in knockout mice compared with controls (76 vs. 29% of the left ventricle, P < 0.05) associated with striking hemorrhage and intense inflammation. Fibrosis normalized for infarct size was markedly reduced (0.006 vs. 0.022 microg hydroxyproline/mg dry weight). Thus, lack of PAI-1 in the heart exerted deleterious effects mediated, at least in part by increased inflammation and hemorrhage and attenuating of fibrosis.
Zaman
A K M Tarikuz
AK
Cardiovascular Research Institute, University of Vermont, Colchester Research Facility, 208 South Park Drive, Colchester, VT 05446, USA.
Fujii
Satoshi
S
Schneider
David J
DJ
Taatjes
Douglas J
DJ
Lijnen
H Roger
HR
Sobel
Burton E
BE
D000818:Animals; D054059:Coronary Occlusion / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency* / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1