Molecular MRI of murine atherosclerotic plaque targeting NGAL: a protein associated with unstable human plaque characteristics
te Boekhorst, B.C.M.; Bovens, S.M.; Hellings, W.E.; van der Kraak, P.H.; van de Kolk, K.W.; Vink, A.; Moll, F.L.; van Oosterhout, M.F.M.; de Vries, J.P.; Doevendans, P.A.F.M.; Goumans, M.J.; de Kleijn, D.P.V.; van Echteld, C.J.A.; Pasterkamp, G.; Sluijter, J.P.G.
(2011) Cardiovascular Research, volume 89, issue 3, pp. 680 - 688
(Article)
Abstract
Aims 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
... read more
target for molecular imaging of atherosclerotic plaques. Methods and results 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. Conclusion 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.
show less
Download/Full Text
Keywords: Atherosclerosis, Matrix metalloproteinases, Macrophages, Contrast agents, Molecular MRI, GELATINASE-ASSOCIATED LIPOCALIN, MATRIX METALLOPROTEINASES, NEUTROPHIL GELATINASE, CAROTID-ENDARTERECTOMY, MYOCARDIAL-INFARCTION, EPITHELIAL-CELLS, CONTRAST AGENTS, IN-VIVO, EXPRESSION, LESIONS, Journal Article, Research Support, Non-U.S. Gov't
ISSN: 0008-6363
Publisher: Oxford University Press
(Peer reviewed)