151. Myeloid β-Catenin Deficiency Exacerbates Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
- Author
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Se-Hyung Park, Fang Wang, Zun Liu, Yipeng Sui, Changcheng Zhou, Murong Ma, Weiwei Lu, and Taesik Gwag
- Subjects
Male ,STAT3 Transcription Factor ,0301 basic medicine ,Time Factors ,Myeloid ,Polarity (physics) ,Cellular differentiation ,Aortic Diseases ,Inflammation ,macrophage ,Diet, High-Fat ,Mice ,03 medical and health sciences ,Cell Movement ,Cell Adhesion ,medicine ,Animals ,Macrophage ,Wnt Signaling Pathway ,Aorta ,beta Catenin ,Mice, Knockout ,Basic Sciences ,Chemistry ,Macrophages ,Wnt signaling pathway ,β-catenin ,Atherosclerosis ,Lipids ,Plaque, Atherosclerotic ,3. Good health ,Cell biology ,Disease Models, Animal ,low-density lipoprotein receptor ,RAW 264.7 Cells ,STAT1 Transcription Factor ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, LDL ,inflammation ,Catenin ,LDL receptor ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Disease Progression ,medicine.symptom ,Cardiology and Cardiovascular Medicine - Abstract
Supplemental Digital Content is available in the text., Objective— The Wnt/β-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/β-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage β-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of β-catenin expression on macrophage functions and atherosclerosis development. Approach and Results— To investigate the role of macrophage canonical Wnt/β-catenin signaling in atherogenesis, we generated β-cateninΔmyeLDLR−/− mice (low-density lipoprotein receptor–deficient mice with myeloid-specific β-catenin deficiency). As expected, deletion of β-catenin decreased macrophage adhesion and migration properties in vitro. However, deficiency of β-catenin significantly increased atherosclerotic lesion areas in the aortic root of LDLR−/− (low-density lipoprotein receptor–deficient) mice without affecting the plasma lipid levels and atherosclerotic plaque composition. Mechanistic studies revealed that β-catenin can regulate activation of STAT (signal transducer and activator of transcription) pathway in macrophages, and ablation of β-catenin resulted in STAT3 downregulation and STAT1 activation, leading to elevated macrophage inflammatory responses and increased atherosclerosis. Conclusions— This study demonstrates a critical role of myeloid β-catenin expression in atherosclerosis by modulating macrophage inflammatory responses.
- Published
- 2018
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