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 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.
Original language | English |
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Pages (from-to) | 680-688 |
Number of pages | 9 |
Journal | Cardiovascular Research |
Volume | 89 |
Issue number | 3 |
DOIs | |
Publication status | Published - Feb 2011 |
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