Influence of the plasminogen activator system on necrosis in acute myocardial infarction: analysis of urokinase- and urokinase receptor-knockout mouse models.

In this study, we investigated the influence of the plasminogen activator system involving urokinase and urokinase receptor on necrosis after acute myocardial infarction. Myocardial infarction and reperfusion were induced in mouse hearts using the in vitro Langendorff model. DNA fragmentation and cleaved caspase-3 activity in urokinase- (uPA-/-) and urokinase receptor-knockout mice (uPAR-/-) were determined and compared with those in wild-type mice using in situ nick-end DNA labeling (TUNEL) and enzyme-linked immunosorbent assays, respectively. Infarct sizes were determined using propidium iodide and fluorescent microspheres. Following regional ischemia and reperfusion, a significant increase in the number of TUNEL-positive nuclei was observed in the ischemic zone in mouse hearts and to a lesser degree in regions remote from the ischemic area in wild-type, uPAR-/-, and uPA-/- groups compared with those in directly removed hearts. No significant differences were observed between uPAR-/- and wild-type mice. Conversely, a significant reduction in DNA fragmentation was observed in ischemic and nonischemic regions after acute myocardial infarction in uPA-/- mice when compared with that in wild-type and uPAR-/- groups. The resulting infarct sizes were significantly smaller in uPA-/- mice than in uPAR-/- and wild-type mice. These data demonstrated the involvement of uPA, but not uPAR, in protecting against necrosis during acute myocardial infarction.
PMID: 31312373 [PubMed]

Source: American Journal of Translational Research - July 19, 2019 Category: Research Tags: Am J Transl Res Source Type: research