Near-infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction

Overview

Journal Circulation

Specialty Cardiology & Vascular Diseases

Date 2005 Apr 6

PMID 15809374

Citations 89

Authors

Jiqiu Chen

Ching-Hsuan Tung

Jennifer R Allport

Si Chen

Ralph Weissleder

Paul L Huang

Affiliations

Soon will be listed here.

Abstract

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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