Abstract |
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.
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Authors | A K M Tarikuz Zaman, Satoshi Fujii, David J Schneider, Douglas J Taatjes, H Roger Lijnen, Burton E Sobel |
Journal | Histochemistry and cell biology
(Histochem Cell Biol)
Vol. 128
Issue 2
Pg. 135-45
(Aug 2007)
ISSN: 0948-6143 [Print] Germany |
PMID | 17576591
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Plasminogen Activator Inhibitor 1
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Topics |
- Animals
- Coronary Occlusion
(etiology, pathology, physiopathology)
- Disease Models, Animal
- Echocardiography
- Inflammation
(metabolism)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Myocardial Infarction
(physiopathology)
- Plasminogen Activator Inhibitor 1
(deficiency, genetics)
- Ventricular Dysfunction, Left
(physiopathology)
- Ventricular Remodeling
(physiology)
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