Near-infrared fluorescent imaging of matrix metalloproteinase activity after myocardial infarction.
BACKGROUND
We used a molecular probe activated by protease cleavage to image expression of matrix metalloproteinases (MMPs) in the heart after myocardial infarction.


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.
Chen
Jiqiu
J
Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass 02129, USA.
Tung
Ching-Hsuan
CH
Allport
Jennifer R
JR
Chen
Si
S
Weissleder
Ralph
R
Huang
Paul L
PL
D000818:Animals; D003952:Diagnostic Imaging; D005456:Fluorescent Dyes; D007259:Infrared Rays; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000138:chemical synthesis / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000201:enzymology* / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology; D015854:Up-Regulation
D005456:Fluorescent Dyes; D015335:Molecular Probes; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse