BMC Cardiovasc Disord. 2026 Jul 11. doi: 10.1186/s12872-026-06275-w. Online ahead of print.
ABSTRACT
BACKGROUND: Aortic dissection (AD) is a life-threatening vascular condition characterized by acute inflammation and structural deterioration of the aortic wall. This study aimed to delineate the immune landscape, particularly T cell-mediated responses, and identify conserved inflammatory mechanisms driving AD pathogenesis across human and murine models.
METHODS: Ascending aortic tissues and plasma were collected from patients with AD and normal controls. CD45⁺ immune cells were isolated using magnetic-activated cell sorting, followed by single-cell RNA sequencing (scRNA-seq) via the 10x Genomics Chromium platform. Data processing and downstream bioinformatics analyses were performed using Cell Ranger and Seurat pipelines, including cell clustering, differential expression, and pathway enrichment analyses. To validate transcriptomic findings, a β-aminopropionitrile (BAPN)-induced AD mouse model was established, and aortic tissues were subjected to eukaryotic transcriptome sequencing. Differentially expressed genes (DEGs) were identified and functionally annotated via GO and KEGG analyses, while transcription factor-target networks were constructed to reveal key regulators. Cross-species integration of human and murine transcriptomic datasets was conducted to identify conserved DEGs and signaling pathways. Quantitative PCR and ELISA were performed on human samples to validate transcriptomic results and assess systemic inflammatory responses.
RESULTS: scRNA-seq analysis revealed a distinct immune landscape in AD tissues characterized by significant T cell enrichment and activation. Disease-associated T cell clusters exhibited elevated expression of cytotoxic and inflammatory genes such as GZMA, GZMB, IFIT1, and IFI6, indicating enhanced adaptive immune activity within the aortic wall. Bulk transcriptomic analysis further demonstrated upregulation of pro-inflammatory mediators (IL1B, CXCL8, CCL2, NFKBIA) and enrichment in immune-related pathways, including TNF, NF-κB, and IL-17 signaling. In the murine AD model, transcriptomic profiling identified 4,427 DEGs, primarily involved in inflammatory responses, leukocyte migration, extracellular matrix remodeling, and apoptosis. Transcription factor analysis highlighted Nfkb1, Jun, Fos, and Stat3 as key regulatory hubs orchestrating these processes. Cross-species integration revealed 51 conserved DEGs between human and mouse datasets, predominantly enriched in IL-17 and cytokine-cytokine receptor interaction pathways. qRT-PCR validation in human aortic tissues confirmed significant upregulation of IL1B, IL6, MAPK10, MAPK12, MMP9, MMP13, S100A8, and S100A9 in AD samples, while ELISA demonstrated elevated serum levels of IFN-γ, IL-10, IL-6, TNF-α, IL-17 A, and IL-8, indicative of a systemic pro-inflammatory state.
CONCLUSION: Collectively, our integrative multi-omics analyses demonstrate that aortic dissection is driven by coordinated immune remodeling involving both adaptive and innate immune cells, accompanied by conserved inflammatory transcriptional programs across human and murine datasets. Despite limited changes in circulating cytokines, tissue-level analyses reveal robust activation of TNF, NF-κB, and IL-17-associated pathways, underscoring the importance of local vascular immune responses in AD pathogenesis.
PMID:42436415 | DOI:10.1186/s12872-026-06275-w