Zhaohui Hu1, Bo Hui2, Xuwei Hou3, Ruhui Liu1, Sergiy Sukhanov4, Xiaohong Liu5. 1. Department of Cardiovascular Diseases, Tongji Hospital of Tongji University Shanghai 200065, P. R. China. 2. Department of Cardiovascular Diseases, Qingdao Municipal Hospital of Qingdao University Qingdao, P. R. China. 3. Department of Cardiology, The University of Missouri School of Medicine Columbia, MO 65201, USA. 4. Heart and Vascular Institute, Tulane University School of Medicine New Orleans, LA 70112, USA. 5. Cardiovascular Department of Internal Medicine, Central Hospital of Karamay Karamay 834000, Xinjiang Uyghur Autonomous Region, P. R. China.
Abstract
BACKGROUND: Macrophage activation and massive foam cell formation are key events in the development of Atherosclerosis (AS). Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1) is an enzyme responsible for DNA repair and redox regulation. Recent studies indicate that APE1 is also involved in inflammatory response. We sought to explore its effect on oxidized low-density lipoprotein (oxLDL) induced macrophage activation and foam cell formation. METHODS: Human macrophage cell line THP-1 cells were cultured and treated with oxLDL. The mRNA and protein levels of inflammatory markers for macrophage activation were measured. Foam cell formation was detected by Oil red O staining. Meanwhile the major cellular receptors responsible for oxLDL uptake and efflux were detected. Chromatin immunoprecipitation-quantitative real time PCR (ChIP-qPCR) and dual luciferase reporter assays were performed to identify the molecular mechanisms through which APE1 affects macrophage activation and foam cell formation. RESULTS: Aberrant APE1 expression dramatically decreases the mRNA and protein of oxLDL-induced inflammatory molecules in THP-1 cells, accompanied by significantly inhibited foam cell formation. Western blot assay showed that down-regulation of LOX1, a receptor of oxLDL, is responsible for the inhibitory effect of APE1 on oxLDL induced macrophage inflammation. ChIP-qPCR assay showed that APE1 inhibits binding of the LOX1 promoter to its transcription factor Oct1, leading to suppression of LOX1. CONCLUSION: Our data confirm the anti-inflammatory properties of APE1 and for the first-time report that APE1 suppresses foam cell formation from macrophages via the oxLDL receptor LOX1. This finding indicates that APE1 can be a therapeutic target for AS prevention. AJTR
BACKGROUND: Macrophage activation and massive foam cell formation are key events in the development of Atherosclerosis (AS). Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1) is an enzyme responsible for DNA repair and redox regulation. Recent studies indicate that APE1 is also involved in inflammatory response. We sought to explore its effect on oxidized low-density lipoprotein (oxLDL) induced macrophage activation and foam cell formation. METHODS:Human macrophage cell line THP-1 cells were cultured and treated with oxLDL. The mRNA and protein levels of inflammatory markers for macrophage activation were measured. Foam cell formation was detected by Oil red O staining. Meanwhile the major cellular receptors responsible for oxLDL uptake and efflux were detected. Chromatin immunoprecipitation-quantitative real time PCR (ChIP-qPCR) and dual luciferase reporter assays were performed to identify the molecular mechanisms through which APE1 affects macrophage activation and foam cell formation. RESULTS: Aberrant APE1 expression dramatically decreases the mRNA and protein of oxLDL-induced inflammatory molecules in THP-1 cells, accompanied by significantly inhibited foam cell formation. Western blot assay showed that down-regulation of LOX1, a receptor of oxLDL, is responsible for the inhibitory effect of APE1 on oxLDL induced macrophage inflammation. ChIP-qPCR assay showed that APE1 inhibits binding of the LOX1 promoter to its transcription factor Oct1, leading to suppression of LOX1. CONCLUSION: Our data confirm the anti-inflammatory properties of APE1 and for the first-time report that APE1 suppresses foam cell formation from macrophages via the oxLDL receptor LOX1. This finding indicates that APE1 can be a therapeutic target for AS prevention. AJTR
Authors: Minghui Qin; Lai Wang; Fuqiang Li; Mingjie Yang; Lei Song; Fang Tian; Ada Yukht; Prediman K Shah; Marc E Rothenberg; Behrooz G Sharifi Journal: Atherosclerosis Date: 2017-05-20 Impact factor: 5.162
Authors: Marieke C S Boshuizen; Marten A Hoeksema; Annette E Neele; Saskia van der Velden; Anouk A J Hamers; Jan Van den Bossche; Esther Lutgens; Menno P J de Winther Journal: Cytokine Date: 2015-10-01 Impact factor: 3.861