| Autor: |
Romanic, Anne M., Harrison, Stephen M., Bao, Weike, Burns-Kurtis, Cynthia L., Pickering, Susan, Gu, Juanli, Grau, Evelyn, Mao, Joyce, Sathe, Ganesh M., Ohlstein, Eliot H., Yue, Tian-Li |
| Předmět: |
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| Zdroj: |
Cardiovascular Research; Jun2002, Vol. 54 Issue 3, p549, 10p |
| Abstrakt: |
Objective: Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia–reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mouse. Methods and results: Standard homologous recombination in embryonic stem cells was used to generate a mouse lacking MMP-9. The left anterior descending coronary artery was occluded for 30 min followed by 24 h reperfusion, and the ischemic and infarct sizes were determined. Targeted deletion of MMP-9 protected the heart from no-flow ischemia–reperfusion-induced myocardial injury. The myocardial infarct size was reduced by 17.5% in MMP-9 heterozygotes (+/−) (P<0.01) and 35.4% in MMP-9 knockout (−/−) mice (P<0.01) versus the wild-type (+/+) mice, respectively. Analysis of MMP activity in myocardial extracts by zymography demonstrated that ischemia–reperfusion-induced expression of proMMP-9 and active MMP-9 was reduced by 77.8% (P<0.01) and 69.1% (P<0.001), respectively, in (+/−) mice compared to (+/+) mice, and was absent in (−/−) animals. The expression of TIMP-1, an endogenous inhibitor of MMP-9, was elevated 4.7-fold (P<0.05) and 21.4-fold (P<0.05) in the (+/−) and (−/−) mice, respectively, compared to (+/+) mice. Immunohistochemical analysis revealed that neutrophils were the primary cellular source of MMP-9, and less neutrophils were detected in the ischemic region of the heart following ischemia–reperfusion in (−/−) mice compared to (+/+) mice. Measurement of myeloperoxidase activity, a marker enzyme of neutrophils, demonstrated a 44% reduction in neutrophils infiltrated into the ischemic myocardium in the (−/−) mice compared to the (+/+) mice (P<0.05). Conclusion: These results suggest that MMP-9 plays an important role in ischemia–reperfusion-induced myocardial infarction and MMP-9 could be a target for prevention or treatment of acute ischemic myocardial injury. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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