The potential of ARL4C and its-mediated genes in atherosclerosis and agent development

Foam cells are the risk factors for atherosclerosis. Recently, ARL4C, a member of the ADP-ribosylation factor family of GTP-binding proteins, was found to promote cholesterol efflux to decrease foam cell formation, suggesting that ARL4C may be a new promising target for the treatment of atherosclero...

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Main Authors: Dan Liu, Jie Wang, Shuangshuang Zhang, Hongfei Jiang, Yudong Wu, Chao Wang, Wujun Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1513340/full
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author Dan Liu
Jie Wang
Shuangshuang Zhang
Hongfei Jiang
Yudong Wu
Chao Wang
Wujun Chen
Wujun Chen
author_facet Dan Liu
Jie Wang
Shuangshuang Zhang
Hongfei Jiang
Yudong Wu
Chao Wang
Wujun Chen
Wujun Chen
author_sort Dan Liu
collection DOAJ
description Foam cells are the risk factors for atherosclerosis. Recently, ARL4C, a member of the ADP-ribosylation factor family of GTP-binding proteins, was found to promote cholesterol efflux to decrease foam cell formation, suggesting that ARL4C may be a new promising target for the treatment of atherosclerosis. In fact, ARL4C regulated the expression of multiple atherosis-related genes, including ABCA1, ALDH1A3, ARF6, ENHO, FLNA, LRP6, OSBPL5, Snail2, and SOX2. Many agents, including ABCA1 agonists (CS-6253, IMM-H007, RG7273, and R3R-01), FLNA antagonist sumifilam, LRP6 inhibitor BI-905677 and agonist SZN-1326, and SOX2 inhibitor STEMVAC, were investigated in clinical trials. Targeting these genes could improve the success rate of drug development in clinical trials. Indeed, many agents could regulate ARL4C expression, including LXR/RXR agonists, Ac-LDL, sucrose, T9-t11-CLA, and miR-26. Downregulation of ARL4C with siRNA and anti-sense oligonucleotide (ASO), such as ASO-1316, is developing in preclinical research for the treatment of lung adenocarcinoma, liver cancer, and colorectal cancer. Thus, ARL4C and its regulated genes may be a potential target for drug development. Thus, we focus on the role of ARL4C and its-mediated genes in atherosclerosis and agent development, which provide insights for the identification, research, and drug development of novel targets.
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spelling doaj-art-c8d800e4e17741cc8b57bd10eb126d1c2025-08-20T01:49:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15133401513340The potential of ARL4C and its-mediated genes in atherosclerosis and agent developmentDan Liu0Jie Wang1Shuangshuang Zhang2Hongfei Jiang3Yudong Wu4Chao Wang5Wujun Chen6Wujun Chen7Guangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai, Guangdong, ChinaAffiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, ChinaAffiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, ChinaAffiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, ChinaAffiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, ChinaAffiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, ChinaGuangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai, Guangdong, ChinaAffiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, ChinaFoam cells are the risk factors for atherosclerosis. Recently, ARL4C, a member of the ADP-ribosylation factor family of GTP-binding proteins, was found to promote cholesterol efflux to decrease foam cell formation, suggesting that ARL4C may be a new promising target for the treatment of atherosclerosis. In fact, ARL4C regulated the expression of multiple atherosis-related genes, including ABCA1, ALDH1A3, ARF6, ENHO, FLNA, LRP6, OSBPL5, Snail2, and SOX2. Many agents, including ABCA1 agonists (CS-6253, IMM-H007, RG7273, and R3R-01), FLNA antagonist sumifilam, LRP6 inhibitor BI-905677 and agonist SZN-1326, and SOX2 inhibitor STEMVAC, were investigated in clinical trials. Targeting these genes could improve the success rate of drug development in clinical trials. Indeed, many agents could regulate ARL4C expression, including LXR/RXR agonists, Ac-LDL, sucrose, T9-t11-CLA, and miR-26. Downregulation of ARL4C with siRNA and anti-sense oligonucleotide (ASO), such as ASO-1316, is developing in preclinical research for the treatment of lung adenocarcinoma, liver cancer, and colorectal cancer. Thus, ARL4C and its regulated genes may be a potential target for drug development. Thus, we focus on the role of ARL4C and its-mediated genes in atherosclerosis and agent development, which provide insights for the identification, research, and drug development of novel targets.https://www.frontiersin.org/articles/10.3389/fphar.2025.1513340/fullatherosclerosischolesterol effluxARL4CABCA1agent development
spellingShingle Dan Liu
Jie Wang
Shuangshuang Zhang
Hongfei Jiang
Yudong Wu
Chao Wang
Wujun Chen
Wujun Chen
The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
Frontiers in Pharmacology
atherosclerosis
cholesterol efflux
ARL4C
ABCA1
agent development
title The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
title_full The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
title_fullStr The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
title_full_unstemmed The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
title_short The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
title_sort potential of arl4c and its mediated genes in atherosclerosis and agent development
topic atherosclerosis
cholesterol efflux
ARL4C
ABCA1
agent development
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1513340/full
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