Lipocalin-2 contributes to experimental atherosclerosis in a stage-dependent manner.
BACKGROUND AND AIMS
Lipocalin-2 (Lcn2) is a glycoprotein which can be secreted by immune cells. Several studies in humans have suggested Lcn2 can be used as a biomarker for the detection of unstable atherosclerotic lesions, partly as it is known to interact with MMP-9.


METHODS
In this study, we generated Ldlr-/-Lcn2-/- mice to assess the functional role of Lcn2 in different stages of atherosclerosis. Atherosclerotic lesions were characterized through histological analysis and myeloid cell populations were examined using flow cytometry.


RESULTS
We show that Ldlr-/-Lcn2-/- mice developed larger atherosclerotic lesions during earlier stages of atherosclerosis and had increased circulating Ly6Chi inflammatory monocytes compared to Ldlr-/- mice. Advanced atherosclerotic lesions from Ldlr-/-Lcn2-/- mice had decreased necrotic core area, suggesting Lcn2 deficiency may affect lesion stability. Furthermore, MMP-9 activity was diminished in plaques from Ldlr-/-Lcn2-/- mice.


CONCLUSIONS
Altogether, these findings suggest that Lcn2 deficiency promotes lesion growth in earlier stages of the disease while it decreases MMP-9 activity and necrotic core size in advanced atherosclerosis.
['Amersfoort|J|J|', 'Schaftenaar|F H|FH|', 'Douna|H|H|', 'van Santbrink|P J|PJ|', 'Kröner|M J|MJ|', 'van Puijvelde|G H M|GHM|', 'Quax|P H A|PHA|', 'Kuiper|J|J|', 'Bot|I|I|']
D000818:Animals D001011:Aorta D001018:Aortic Diseases D050197:Atherosclerosis D059305:Diet, High-Fat D004195:Disease Models, Animal D018450:Disease Progression D005260:Female D020022:Genetic Predisposition to Disease D000071068:Lipocalin-2 D020780:Matrix Metalloproteinase 9 D018345:Mice, Knockout D009000:Monocytes D009336:Necrosis D010641:Phenotype D058226:Plaque, Atherosclerotic D011973:Receptors, LDL D013997:Time Factors
Lipocalin-2 Atherosclerosis MMP-9 Monocytes Necrotic core