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.
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.
Authors: L Roten; S Nemoto; J Simsic; M L Coker; V Rao; S Baicu; G Defreyte; P J Soloway; M R Zile; F G Spinale Journal: J Mol Cell Cardiol Date: 2000-01 Impact factor: 5.000
Authors: C Fernandez-Patron; M A Martinez-Cuesta; E Salas; G Sawicki; M Wozniak; M W Radomski; S T Davidge Journal: Thromb Haemost Date: 1999-12 Impact factor: 5.249
Authors: L Lu; Z Gunja-Smith; J F Woessner; P C Ursell; T Nissen; R E Galardy; Y Xu; P Zhu; G G Schwartz Journal: Am J Physiol Heart Circ Physiol Date: 2000-08 Impact factor: 4.733
Authors: A Ducharme; S Frantz; M Aikawa; E Rabkin; M Lindsey; L E Rohde; F J Schoen; R A Kelly; Z Werb; P Libby; R T Lee Journal: J Clin Invest Date: 2000-07 Impact factor: 14.808