This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wallis de Vries, B. M. Articles by Zeebregts, C. J. Search for Related Content PubMed PubMed Citation Articles by Wallis de Vries, B. M. Articles by Zeebregts, C. J. Related Collections Cardiovascular imaging agents/Techniques Imaging Smooth muscle proliferation and differentiation Carotid Stenosis Other imaging Carotid endarterectomy

(Circulation. 2009;119:e534-e536.)
© 2009 American Heart Association, Inc.

Images in Cardiovascular Medicine

Multispectral Near-Infrared Fluorescence Molecular Imaging of Matrix Metalloproteinases in a Human Carotid Plaque Using a Matrix-Degrading Metalloproteinase–Sensitive Activatable Fluorescent Probe

Bastiaan M. Wallis de Vries, MD^*; Jan-Luuk Hillebrands, PhD^*; Gooitzen M. van Dam, MD, PhD; René A. Tio, MD, PhD; Johannes S. de Jong, MD, PhD; Riemer H.J.A. Slart, MD, PhD; Clark J. Zeebregts, MD, PhD

From the Departments of Surgery (B.M.W.d.V., G.M.v.D., J.S.d.J., C.J.Z.) and Cell Biology (J.L.H.), University of Groningen; and Departments of Cardiology (R.A.T.) and Nuclear Medicine and Molecular Imaging (R.H.J.A.S.) and Cardiovascular Imaging Group Groningen (R.A.T., R.H.J.A.S., C.J.Z.) and BioOptical Imaging Center Groningen (G.M.v.D.), University Medical Center Groningen, Groningen, the Netherlands.

Correspondence to C.J. Zeebregts, MD, PhD, Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, PO Box 30 001, 9700 RB Groningen, the Netherlands. E-mail czeebregts@hotmail.com

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Formation of unstable atherosclerotic plaque in the internal carotid artery carries a high risk for emboli and subsequent cerebral ischemic events. The fibrous cap of such a plaque may become thin and rupture as a result of the depletion of matrix components through the activation of proteolytic enzymes such as matrix-degrading proteinases. Enhanced matrix breakdown has been attributed primarily to a family of matrix-degrading metalloproteinases (MMPs) that are highly concentrated in atherosclerotic plaques by inflammatory cells (eg, macrophages, foam cells), smooth muscle cells and endothelial cells.¹

Elevated serum MMP-9 concentration is associated with carotid plaque instability and the presence of infiltrated macrophages.² Furthermore, analysis of the presence of MMP-9 protein by ELISA within excised carotid plaques revealed high MMP-9 protein mass in calcified segments at or near the carotid bifurcation and in segments with intraplaque hemorrhage. Gelatin zymography showed an increased gelatinase activity of MMP-9 in these segments.³ These data favor the important role of MMP-9 in the pathogenesis of plaque instability. We analyzed the topographic distribution of MMPs within an excised human carotid plaque by applying multispectral near-infrared fluorescence (NIRF) imaging (IVIS Spectrum, Caliper Life Sciences, Hopkinton, Mass).

A surgical endarterectomy was performed on a 74-year-old women with a left-sided, symptomatic, >70% carotid stenosis. Immediately after endarterectomy, the plaque was placed in PBS and transported to the NIRF system. The plaque was then stretched out and fixed on a silicon plate with 25G needles. A PBS NIRF image was generated from both the intraluminal and extraluminal side of the . . . [Full Text of this Article]