Liu Dan, Wang Jie, Zhang Shuangshuang, Jiang Hongfei, Wu Yudong, Wang Chao, Chen Wujun
Guangdong Provincial People's Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai, Guangdong, China.
Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, Shandong, China.
Front Pharmacol. 2025 Mar 19;16:1513340. doi: 10.3389/fphar.2025.1513340. eCollection 2025.
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.
泡沫细胞是动脉粥样硬化的危险因素。最近，人们发现GTP结合蛋白的ADP核糖基化因子家族成员ARL4C可促进胆固醇流出，减少泡沫细胞形成，这表明ARL4C可能是治疗动脉粥样硬化的一个新的有前景的靶点。事实上，ARL4C调节多个与动脉粥样硬化相关基因的表达，包括ABCA1、ALDH1A3、ARF6、ENHO、FLNA、LRP6、OSBPL5、Snail2和SOX2。许多药物，包括ABCA1激动剂（CS-6253、IMM-H007、RG7273和R3R-01）、FLNA拮抗剂sumifilam、LRP6抑制剂BI-905677和激动剂SZN-1326，以及SOX2抑制剂STEMVAC，都在临床试验中进行了研究。针对这些基因可以提高临床试验中药物开发的成功率。确实，许多药物可以调节ARL4C的表达，包括LXR/RXR激动剂、乙酰化低密度脂蛋白、蔗糖、反式-9，反式-11-共轭亚油酸和miR-26。用小干扰RNA和反义寡核苷酸（ASO），如ASO-1316，下调ARL4C的表达正在肺癌、肝癌和结直肠癌治疗的临床前研究中开展。因此，ARL4C及其调控的基因可能是药物开发的潜在靶点。因此，我们关注ARL4C及其介导的基因在动脉粥样硬化和药物开发中的作用，这为新型靶点的识别、研究和药物开发提供了思路。
