on April 4, 2005
Published online before print April 4, 2005, doi: 10.1161/01.CIR.0000160936.91849.9F
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Submitted on November 19, 2004
From the Cardiovascular Research Center and Cardiology Division (J.C., S.C., P.L.H.) and the Center for Molecular Imaging Research (C.-H.T., J.R.A., R.W.), Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass.
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.
Accepted on December 27, 2004
Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction
Jiqiu Chen MD,
Key words: matrix metalloproteinases • myocardial infarction • imaging • gelatinase • remodeling
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Circulation 2005 111: 1730-1732.
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