Journal
CIRCULATION
Volume 111, Issue 14, Pages 1800-1805Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000160936.91849.9F
Keywords
matrix metalloproteinases; myocardial infarction; imaging; gelatinase; remodeling
Funding
- NCI NIH HHS [P50 CA086355, CA-86355] Funding Source: Medline
- NHLBI NIH HHS [HL-52818, R01 HL057818, R01 HL057818-09] Funding Source: Medline
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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.
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