TY - JOUR
T1 - Molecular MRI of murine atherosclerotic plaque targeting NGAL: a protein associated with unstable human plaque characteristics
AU - Boekhorst, Bernard C. M. Te
AU - Bovens, Sandra M.
AU - Hellings, Willem E.
AU - van der Kraak, Petra H.
AU - van de Kolk, Kees W. A.
AU - Vink, Aryan
AU - Moll, Frans L.
AU - van Oosterhout, Matthijs F. M.
AU - de Vries, Jean-Paul P. M.
AU - Doevendans, Pieter A.
AU - Goumans, Marie-Jose
AU - de Kleijn, Dominique P.
AU - van Echteld, Cees J. A.
AU - Pasterkamp, Gerard
AU - Sluijter, Joost P. G.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Matrix metalloproteinases
KW - Macrophages
KW - Contrast agents
KW - Molecular MRI
U2 - 10.1093/cvr/cvq340
DO - 10.1093/cvr/cvq340
M3 - Article
C2 - 21030534
SN - 0008-6363
VL - 89
SP - 680
EP - 688
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 3
ER -