Related Experiment Video
Updated: May 16, 2025
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
The potential of ARL4C and its-mediated genes in atherosclerosis and agent development
Dan Liu1, Jie Wang2, Shuangshuang Zhang2
1Guangdong Provincial People's Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai, Guangdong, China.
Abstract:
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.
Insights
ARL4C protein promotes cholesterol efflux, reducing foam cell formation and atherosclerosis risk. Targeting ARL4C and its related genes offers a promising new strategy for developing effective atherosclerosis treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Foam cells are key risk factors in atherosclerosis development.
- ARL4C, an ADP-ribosylation factor family protein, influences cholesterol efflux and foam cell formation.
- ARL4C presents a potential therapeutic target for atherosclerosis.
Purpose of the Study:
- To investigate the role of ARL4C in atherosclerosis.
- To explore ARL4C-regulated genes as potential drug targets.
- To review agents targeting ARL4C and its associated pathways for atherosclerosis treatment.
Main Methods:
- Literature review of ARL4C function in atherosclerosis.
- Analysis of ARL4C-regulated atherosis-related genes (e.g., ABCA1, LRP6, SOX2).
- Examination of therapeutic agents targeting these genes and ARL4C.
Main Results:
- ARL4C promotes cholesterol efflux, mitigating foam cell accumulation.
- ARL4C regulates multiple genes implicated in atherosclerosis.
- Various agents targeting ARL4C or its downstream genes are under investigation.
- ARL4C downregulation strategies (siRNA, ASO) show preclinical promise for other cancers.
Conclusions:
- ARL4C and its regulated genes represent significant potential targets for novel atherosclerosis therapies.
- Targeting ARL4C-mediated pathways could enhance the success rate of drug development.
- Further research into ARL4C is crucial for identifying and developing new treatments for atherosclerosis.
Related Concept Videos
01:28Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
01:38Inflammation