New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis

Wujun Chen,1 Shuai Wang,2 Dongming Xing1,3 1Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, People’s Republic of China; 2School of Medical Imaging, Radiotherapy Department of Affiliated Hospital, Weifang Medica...

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Autores principales:	Chen W, Wang S, Xing D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	atherosclerosis inflammatory ape1/ref-1 abca1 cholesterol efflux. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8f53c696b41e4dc0a6e24242b9207f92
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spelling	oai:doaj.org-article:8f53c696b41e4dc0a6e24242b9207f922021-12-02T18:02:56ZNew Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis1178-7031https://doaj.org/article/8f53c696b41e4dc0a6e24242b9207f922021-10-01T00:00:00Zhttps://www.dovepress.com/new-horizons-for-the-roles-and-association-of-ape1ref-1-and-abca1-in-a-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Wujun Chen,1 Shuai Wang,2 Dongming Xing1,3 1Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, People’s Republic of China; 2School of Medical Imaging, Radiotherapy Department of Affiliated Hospital, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3School of Life Sciences, Tsinghua University, Beijing, 100084, People’s Republic of ChinaCorrespondence: Dongming XingCancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, People’s Republic of ChinaTel +86-532- 82991017Email xdm_tsinghua@163.comShuai WangSchool of Medical Imaging, Radiotherapy Department of Affiliated Hospital, Weifang Medical University, Weifang, Shandong, People’s Republic of ChinaTel +86-536-8462228Email sdwftcmws@163.comAbstract: Atherosclerosis is the leading cause of death worldwide. APE1/Ref-1 and ABCA1 play key roles in the progression of atherosclerosis. APE1/Ref-1 suppresses atherosclerosis via multiple mechanisms, including reducing the IL-6-, TNF-α-, and IL-1β-mediated proinflammatory responses, suppressing ROS-mediated oxidant activity and Bax/Bcl-2-mediated vascular calcification and apoptosis, and reducing LOX-1-mediated cholesterol uptake. However, APE1/Ref-1 also promotes atherosclerosis by increasing the activity of the NK-κB and S1PR1 pathways. APE1/Ref-1 localizes to the nucleus, cytoplasm, and mitochondria and can be secreted from the cell. APE1/Ref-1 localization is dynamically regulated by the disease state and may be responsible for its proatherogenic and antiatherogenic effects. ABCA1 promotes cholesterol efflux and anti-inflammatory responses by binding to apoA-I and regulates apoptotic cell clearance and HSPC proliferation to protect against inflammatory responses. Interestingly, in addition to mediating these functions, ABCA1 promotes the secretion of acetylated APE1/Ref-1 (AcAPE1/Ref-1), a therapeutic target, which protects against atherosclerosis development. The APE1/Ref-1 inhibitor APX3330 is being evaluated in a phase II clinical trial. The LXR agonist LXR-623 (WAY-252623) is an agonist of ABCA1 and the first LXR-targeting compound to be evaluated in clinical trials. In this article, we review the roles of ABCA1 and APE1/Ref-1 in atherosclerosis and focus on new insights into the ABCA1-APE1/Ref-1 axis and its potential as a novel therapeutic target in atherosclerosis.Keywords: atherosclerosis, inflammatory, APE1/Ref-1, ABCA1, cholesterol effluxChen WWang SXing DDove Medical Pressarticleatherosclerosisinflammatoryape1/ref-1abca1cholesterol efflux.PathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 5251-5271 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atherosclerosis inflammatory ape1/ref-1 abca1 cholesterol efflux. Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	atherosclerosis inflammatory ape1/ref-1 abca1 cholesterol efflux. Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Chen W Wang S Xing D New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis
description	Wujun Chen,1 Shuai Wang,2 Dongming Xing1,3 1Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, People’s Republic of China; 2School of Medical Imaging, Radiotherapy Department of Affiliated Hospital, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3School of Life Sciences, Tsinghua University, Beijing, 100084, People’s Republic of ChinaCorrespondence: Dongming XingCancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, People’s Republic of ChinaTel +86-532- 82991017Email xdm_tsinghua@163.comShuai WangSchool of Medical Imaging, Radiotherapy Department of Affiliated Hospital, Weifang Medical University, Weifang, Shandong, People’s Republic of ChinaTel +86-536-8462228Email sdwftcmws@163.comAbstract: Atherosclerosis is the leading cause of death worldwide. APE1/Ref-1 and ABCA1 play key roles in the progression of atherosclerosis. APE1/Ref-1 suppresses atherosclerosis via multiple mechanisms, including reducing the IL-6-, TNF-α-, and IL-1β-mediated proinflammatory responses, suppressing ROS-mediated oxidant activity and Bax/Bcl-2-mediated vascular calcification and apoptosis, and reducing LOX-1-mediated cholesterol uptake. However, APE1/Ref-1 also promotes atherosclerosis by increasing the activity of the NK-κB and S1PR1 pathways. APE1/Ref-1 localizes to the nucleus, cytoplasm, and mitochondria and can be secreted from the cell. APE1/Ref-1 localization is dynamically regulated by the disease state and may be responsible for its proatherogenic and antiatherogenic effects. ABCA1 promotes cholesterol efflux and anti-inflammatory responses by binding to apoA-I and regulates apoptotic cell clearance and HSPC proliferation to protect against inflammatory responses. Interestingly, in addition to mediating these functions, ABCA1 promotes the secretion of acetylated APE1/Ref-1 (AcAPE1/Ref-1), a therapeutic target, which protects against atherosclerosis development. The APE1/Ref-1 inhibitor APX3330 is being evaluated in a phase II clinical trial. The LXR agonist LXR-623 (WAY-252623) is an agonist of ABCA1 and the first LXR-targeting compound to be evaluated in clinical trials. In this article, we review the roles of ABCA1 and APE1/Ref-1 in atherosclerosis and focus on new insights into the ABCA1-APE1/Ref-1 axis and its potential as a novel therapeutic target in atherosclerosis.Keywords: atherosclerosis, inflammatory, APE1/Ref-1, ABCA1, cholesterol efflux
format	article
author	Chen W Wang S Xing D
author_facet	Chen W Wang S Xing D
author_sort	Chen W
title	New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis
title_short	New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis
title_full	New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis
title_fullStr	New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis
title_full_unstemmed	New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis
title_sort	new horizons for the roles and association of ape1/ref-1 and abca1 in atherosclerosis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/8f53c696b41e4dc0a6e24242b9207f92
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New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis

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