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 LdlrLcn2 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 LdlrLcn2 mice developed larger atherosclerotic lesions during earlier stages of atherosclerosis and had increased circulating Ly6C inflammatory monocytes compared to Ldlr mice. Advanced atherosclerotic lesions from LdlrLcn2 mice had decreased necrotic core area, suggesting Lcn2 deficiency may affect lesion stability. Furthermore, MMP-9 activity was diminished in plaques from LdlrLcn2 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.