Molecular MRI of murine atherosclerotic plaque targeting NGAL: a protein associated with unstable human plaque characteristics

Bernard C. M. Te Boekhorst*, Sandra M. Bovens, Willem E. Hellings, Petra H. van der Kraak, Kees W. A. van de Kolk, Aryan Vink, Frans L. Moll, Matthijs F. M. van Oosterhout, Jean-Paul P. M. de Vries, Pieter A. Doevendans, Marie-Jose Goumans, Dominique P. de Kleijn, Cees J. A. van Echteld, Gerard Pasterkamp, Joost P. G. Sluijter

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is an effector molecule of the innate immune system. One of its actions is the prolongation of matrix metalloproteinase-9 (MMP-9) activity by the formation of a degradation-resistant NGAL/MMP-9 complex. We studied NGAL in human atherosclerotic lesions and we examined whether NGAL could act as a target for molecular imaging of atherosclerotic plaques.Increased levels of NGAL and the NGAL/MMP-9 complex were associated with high lipid content, high number of macrophages, high interleukin-6 (IL-6) and IL-8 levels, and low smooth muscle cell content in human atherosclerotic lesions obtained during carotid endarterectomy (n= 122). Moreover, plaque levels of NGAL tended to be higher when intra-plaque haemorrhage (IPH) or luminal thrombus was present (n= 77) than without the presence of IPH or thrombus (n= 30). MMP-9 and -8 activities were strongly related to NGAL levels. The enhancement on magnetic resonance (MR) images of the abdominal aorta of ApoE(-/-)/eNOS(-/-) mice was observed at 72 h after injection of NGAL/24p3-targeted micelles. The specificity of these results was validated by histology, and co-localization of micelles, macrophages, and NGAL/24p3 was observed.NGAL is highly expressed in atheromatous human plaques and associated with increased MMP-9 activity. NGAL can be detected in murine atherosclerotic arteries using targeted high-resolution MR imaging. Therefore, we conclude that NGAL might serve as a novel imaging target for the detection of high-risk plaques.
Original languageEnglish
Pages (from-to)680-688
JournalCardiovascular Research
Volume89
Issue number3
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Atherosclerosis
  • Matrix metalloproteinases
  • Macrophages
  • Contrast agents
  • Molecular MRI

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