J Amersfoort1, F H Schaftenaar2, H Douna2, P J van Santbrink2, M J Kröner2, G H M van Puijvelde2, P H A Quax3, J Kuiper2, I Bot2. 1. Division of Biotherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands. Electronic address: j.amersfoort@lacdr.leidenuniv.nl. 2. Division of Biotherapeutics, LACDR, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands. 3. Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
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.
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 Lcn2deficiency may affect lesion stability. Furthermore, MMP-9 activity was diminished in plaques from Ldlr-/-Lcn2-/- mice. CONCLUSIONS: Altogether, these findings suggest that Lcn2deficiency promotes lesion growth in earlier stages of the disease while it decreases MMP-9 activity and necrotic core size in advanced atherosclerosis.
Authors: Jacob Amersfoort; Hidde Douna; Frank H Schaftenaar; Amanda C Foks; Mara J Kröner; Peter J van Santbrink; Gijs H M van Puijvelde; Ilze Bot; Johan Kuiper Journal: Front Immunol Date: 2018-12-12 Impact factor: 7.561
Authors: Ming Chen; Yi Li; Xiang Huang; Ya Gu; Shang Li; Pengbin Yin; Licheng Zhang; Peifu Tang Journal: Bone Res Date: 2021-03-22 Impact factor: 13.567