What question did this study set out to answer?

The study aims to explore programmed cell death biomarkers in aortic dissection to identify new treatment targets.

March 30, 2026Open Access

IL6/IL10/TLR4 Govern Immunogenic Cell Death in Aortic Dissection

Key Result

IL6 (11.8-fold upregulated), IL10 (26.1-fold upregulated), and TLR4 (0.38-fold downregulated) emerged as central regulators of programmed cell death in aortic dissection pathogenesis.

Key Points

The study aims to explore programmed cell death biomarkers in aortic dissection to identify new treatment targets.
Conducted multiomics analysis integrating transcriptome sequencing from aortic tissues.
Intersected differentially expressed genes with programmed cell death-related genes.
Characterized biomarkers using protein-protein interaction networks and immune profiling.
Identified drug candidates through drug-target mapping.
Identified three key biomarkers: IL6 (11.8-fold upregulated), IL10 (26.1-fold upregulated), and TLR4 (0.38-fold downregulated).
The biomarkers were enriched in immunoregulatory pathways and showed significant correlations with immune cells.
Uncovered a transcription factor and miRNA regulatory network influencing biomarker expression.
Identified 91 potential repurposable drugs, including dual IL6/IL10 inhibitors.

Structured PICO

Population

Transcriptome sequencing data from 8 aortic dissection (AD) tissues and 5 control aortic tissues

Comparator

5 control aortic tissues

Outcome

Identification of programmed cell death-related biomarkers and therapeutic targetssurrogate

Multiomics analysis identifies IL6, IL10, and TLR4 as central regulators of programmed cell death in aortic dissection, highlighting them as potential therapeutic targets.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Background Aortic dissection (AD), a life‐threatening cardiovascular emergency, poses a significant threat to global cardiovascular health. Emerging evidence implicates programmed cell death (PCD) as a critical driver of AD pathogenesis, yet the molecular mechanisms remain poorly defined. This study systematically investigates PCD‐related biomarkers in AD to identify novel therapeutic targets. Methods Multiomics analysis integrated transcriptome sequencing data from eight AD and five control aortic tissues. Differentially expressed genes (DEmRNAs, n = 3094) were intersected with 1574 programmed cell death–related genes (PCD‐RGs) to identify candidate biomarkers. Protein–protein interaction (PPI) networks, functional enrichment, immune infiltration profiling, and drug‐target prediction were employed to characterize key molecular drivers. Results Three PCD‐associated biomarkers were identified: IL6 (11.8‐fold upregulated), IL10 (26.1‐fold upregulated), and TLR4 (0.38‐fold downregulated). These biomarkers exhibited significant enrichment in immunoregulatory pathways including “MYC Targets V1” (FDR < 0.05), with IL10 showing strong immune microenvironment correlations (memory B cells: r = 0.62; endothelial cells: r = −0.58). Regulatory network analysis revealed 58 transcription factors (STAT1/SP1/IRF8) and six key miRNAs (e.g., miR‐204‐5p) orchestrating biomarker expression. Drug‐target mapping identified 91 repurposable agents, including etanercept‐szzs (dual IL6/IL10 inhibitor) and TLR4‐modulating compounds. Conclusion This study establishes IL6, IL10, and TLR4 as central regulators of PCD‐mediated AD pathogenesis, implicating immune–vascular crosstalk and immunogenic cell death as therapeutic entry points. The identified biomarker network and drug candidates provide a translational framework for developing precision therapies against AD.