Near-infrared fluorescent Imaging of matrix metalloproteinase activity after myocardial infarction

Article

关键词: IN-VIVO;    REPERFUSION INJURY;    TARGETED DELETION;    TISSUE INHIBITORS;    HEART-FAILURE;    FAILING HEART;    MICE;    ISCHEMIA;    ACTIVATION;    EXPRESSION;   

DOI  :  10.1161/01.CIR.0000160936.91849.9F

来源: SCIE

【 摘 要 】

Background-We used a molecular probe activated by protease cleavage to image expression of matrix metalloproteinases ( MMPs) in the heart after myocardial infarction. Methods and Results-We synthesized and characterized a near-infrared fluorescent (NIRF) probe that is activated by proteolytic cleavage by MMP2 and MMP9. The NIRF probe was injected into mice at various time points up to 4 weeks after myocardial infarction induced by ligation of the left anterior descending coronary artery. NIRF imaging of MMP activity increased in the infarct region, with maximal expression at 1 to 2 weeks, persisting to 4 weeks. Zymography and real-time polymerase chain reaction analysis showed that MMP9 expression is increased at 2 to 4 days, and MMP2 expression is increased at 1 to 2 weeks. Dual-label confocal microscopy showed colocalization of NIRF imaging with neutrophils on day 2, and flow cytometric analysis confirmed that NIRF signal is associated with leukocytes in the infarct zone. Conclusions-This study demonstrates that the activity of MMPs in the myocardium may be imaged by use of specific activity-dependent molecular probes.

【 授权许可】

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