Abstract 1721: NGAL and NGAL/MMP-9 Complex in Carotid Plaques and Abdominal Aortic Aneurysms
Background Neutrophil gelatinase-associated lipocalin (NGAL) preserves matrix metalloproteinase (MMP)-9 activity via complex formation. This leads to sustained activity of MMP-9, which could give rise to plaque destabilization, expansive remodeling and aneurysm rupture. In this study, we examined NGAL and MMP-9 in the vascular wall of abdominal aortic aneurysms (AAA) and carotid plaques in relation to atherosclerotic plaque characteristics.
Methods Activity levels of the NGAL/MMP-9 complex (135 kD) were determined by gelatin zymography in 82 carotid endarterectomy specimens and 21 specimens of the ventral aortic aneurysm wall, which were obtained during AAA surgery. In a subset of 23 carotid plaques, NGAL expression levels were determined by ELISA. The culprit lesions of the carotid plaques were stained for NGAL, CD68, alpha-actin, CD34, picro-sirius red, elastin and HE. In addition, interleukin (IL)-6 and -8 levels (Multiplex) and MMP-2, -8, -9 activities (Biotrak) were determined. Mammary arteries (n=9) and macroscopically normal abdominal aortas (n=4) served as a control.
Results Gelatinolytic activity levels of the NGAL/MMP-9 complex were higher in carotid plaques and abdominal aortic aneurysms compared to non-diseased aortas: 14.4 (p=0.01) and 6.8 (p=0.002) fold increase, respectively. Compared to mammary arteries, NGAL/MMP-9 activity levels were increased 5.3 fold in carotid plaques (p=0.004) and 2.5 fold in aneurysm wall (p=0.006). In carotid plaques, NGAL was mainly expressed by macrophages, but also some co-localization with smooth muscle cells and CD34+ neo-vessels was observed. High NGAL/MMP-9 activity was associated with unstable plaque characteristics: high fat content (p=0.002), high IL-8 levels (p=0.005), and low smooth muscle cell content (p=0.047). Gelatinolytic activity levels of the NGAL/MMP-9 complex and NGAL expression levels were strongly related to total MMP-9 activity (p=0.003), but not to MMP-2 or MMP-8 activities.
Conclusion The NGAL/MMP-9 complex and single NGAL are highly expressed in unstable carotid plaques and the wall of abdominal aortic aneurysms and show a strong relation with total MMP-9 activity, suggesting a possible role for NGAL in plaque destabilization and expansive vascular remodeling.