Comorbidity Network of Heart Failure and Vascular Dementia:Integrating Single-Cell Multi-Omics with FOXC1-based Drug Discovery
10.3870/j.issn.1672-0741.25.04.016
- VernacularTitle:心力衰竭与血管性痴呆共病网络:整合单细胞多组学与靶向FOXC1药物筛选
- Author:
Tianjiao XIA
1
;
Tianqi ZHANG
;
Bijie WANG
Author Information
1. 武汉科技大学医学院,职业危害识别与控制湖北省重点实验室,环境毒理学实验室,武汉 430065
- Publication Type:Journal Article
- Keywords:
vascular dementia;
heart failure;
single-cell transcriptomic;
forkhead box C1;
Qingdainone
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(4):498-506
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate shared mechanisms and therapeutic targets between heart failure(HF)and vascular de-mentia(VaD),and identify natural compounds for dual-organ protection.Methods Single-cell data(8 samples)from GEO were processed via Seurat for clustering.Through CellChat,inter-organ communication was constructed,and top 95%ligand-receptor pairs were analyzed by KEGG enrichment.Bulk RNA-seq(70 samples)underwent differential gene(limma)and immune infiltra-tion(CIBERSORT)analyses.31186 compounds from TCMbank werescreened by AutoDock Vina,followed by molecular dynam-ics validation.Results HF fibroblasts(43.75%,7 subclusters)and VaD oligodendrocytes(76.57%,6 subclusters)dominated re-spective tissues.Cross-disease integration revealed HF-driven fibrosis(COLLAGEN)and VaD-associated neuroinflammation(SPP1),converging on PI3K-Akt and ECM pathways.HF-specific markers(TNXB/THBS4/COL1 A2)and VaD signatures(SPP1/PDGFC/TGFA)were identified,with FOXC1 identified as a shared transcriptional regulator.B cell activation character-ized immune dysregulation.Among 8 FOXC1 inhibitors,Qingdainone showed optimal binding[affinity:-9.0 kcal/mol;RMSD:(0.2±0.06)nm].Conclusion This study uncovers fibrosis-neuroinflammation crosstalk in HF-VaD comorbidity and proposes Qingdainone as a FOXC1-targeting therapeutic candidate.
