Journal Article Epublish
PubMed: 42763524 DOI: 10.1016/j.gendis.2026.102167
Single-cell sequencing-guided discovery of narciclasine as a dual VCAM-1/ICAM-1 inhibitor for atherosclerosis management.
Genes Dis 14(1):102167
Authors: Yang Wang, Zhen Cao, Huai Lan, Bo Li, Guixue Wang, Qingmei Chen
Affiliations
- College of Environment and Ecology, Chongqing University, Chongqing 400044, China. Department of Cardiology, Chongqing University Jiangjin Hospital, Jiangjin Central Hospital of Chongqing, Chongqing 402260, China.
- College of Environment and Ecology, Chongqing University, Chongqing 400044, China.
- Department of Cardiology, Chongqing University Jiangjin Hospital, Jiangjin Central Hospital of Chongqing, Chongqing 402260, China.
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, National Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China.
- Jinfeng Laboratory, Chongqing 401329, China.
Abstract
Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality worldwide, with current treatments focused primarily on reducing low-density lipoprotein levels while failing to repair damaged endothelial cells, thus highlighting the urgent need for novel therapeutic drugs. To address this challenge, we analyzed human AS patient single-cell RNA sequencing datasets to identify disease-driving genes and then employed connectivity map analysis to screen for potential therapeutic compounds. Using network pharmacology and machine learning to predict core drug targets, the study validated drug-target interactions through molecular docking, molecular dynamics simulations, and surface plasmon resonance analysis, with experimental validation conducted using endothelial cell damage models and ApoE -/- atherosclerotic mice. The integrative approach successfully identified narciclasine as a promising therapeutic compound that targets vascular cell adhesion molecule 1 and intercellular adhesion molecule-1 (VCAM-1/ICAM-1) for AS treatment, with molecular studies confirming strong binding affinity and experimental validation demonstrating significant alleviation of endothelial dysfunction through downregulation of VCAM-1/ICAM-1 expression and reduction of aortic plaque burden in mouse models. This multiplatform methodology combining single-cell sequencing, network pharmacology, machine learning, computational simulation, and experimental validation provides a robust framework for drug discovery while positioning narciclasine as a promising therapeutic candidate warranting clinical investigation for AS treatment.
MeSH
Cells, Vascular Cell Adhesion Molecule-1, Tissue Adhesions, Pharmaceutical Preparations, Machine Learning, Pharmacology, Endothelial Cells, Atherosclerosis, Therapeutics, Learning, Intercellular Adhesion Molecule-1