Journal article
Shared inflammation in takotsubo syndrome and sepsis: Lipocalin-2 mediates neutrophil infiltration and cardiac damage
Cytokine (Philadelphia, Pa.), Vol.198, 157102
02/2026
DOI: 10.1016/j.cyto.2025.157102
PMID: 41475067
Abstract
Takotsubo syndrome (TTS) and sepsis often co-occur with poor outcomes, yet their underlying molecular mechanisms remain to be elucidated. Transcriptomic analysis is employed to detect diagnostic biomarkers and reveal shared pathophysiological mechanisms in sepsis-associated TTS.
Myocardial gene expression data (TTS, sepsis, and controls) from GEO were analyzed to identify shared differentially expressed genes. WGCNA and PPI networks were used for candidate gene selection. Key genes were further refined using random forest and LASSO algorithms. Immune cell infiltration was assessed using CIBERSORT. Myocardial injury and gene expression in rat models were evaluated using HE staining, TUNEL assay, immunohistochemistry, qPCR, and Western blotting. Clinical validation was conducted using plasma samples from the China TTS Registry. t-tests and ANOVA were conducted via GraphPad Prism 8 software. A P-value < 0.05 was considered statistically significant.
Lipocalin-2 (LCN2) was recognized as an important biomarker through WGCNA, PPI network analysis, and machine learning algorithms, showing strong predictive performance. Its expression was significantly associated with neutrophil infiltration and myocardial injury in TTS. Consistent with the bioinformatics findings, the TTS-sepsis comorbidity model showed elevated mRNA and protein levels of LCN2 in myocardial tissue, accompanied by increased neutrophil infiltration and severe cardiac injury. Clinical validation confirmed elevated plasma LCN2 levels in patients with sepsis-associated TTS, correlating with neutrophil counts, NT-proBNP, and cTnI levels.
LCN2 is identified as a key inflammatory mediator linking neutrophil-driven inflammation to myocardial injury in sepsis-associated TTS, with dual potential as a diagnostic biomarker and therapeutic target.
Details
- Title: Subtitle
- Shared inflammation in takotsubo syndrome and sepsis: Lipocalin-2 mediates neutrophil infiltration and cardiac damage
- Creators
- Yuxi HuangPiaorong Zeng - First Affiliated Hospital of Jinan UniversityTianmin Liu - Fifth Affiliated Hospital of Sun Yat-sen UniversityMei Xu - Fifth Affiliated Hospital of Sun Yat-sen UniversityWenyi Tang - Fifth Affiliated Hospital of Sun Yat-sen UniversityFangyuan Cheng - Fifth Affiliated Hospital of Sun Yat-sen UniversityZhijuan Zhou - Fifth Affiliated Hospital of Sun Yat-sen UniversityBairong Chen - Fifth Affiliated Hospital of Sun Yat-sen UniversityKan Liu - Washington University in St. LouisTouKun Chong - Kiang Wu HospitalJian Chen
- Resource Type
- Journal article
- Publication Details
- Cytokine (Philadelphia, Pa.), Vol.198, 157102
- DOI
- 10.1016/j.cyto.2025.157102
- PMID
- 41475067
- NLM abbreviation
- Cytokine
- ISSN
- 1096-0023
- eISSN
- 1096-0023
- Publisher
- Elsevier
- Grant note
- Science and Technology Development Fund, Macau SAR: 0117/2019/A3 Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province: 2023LSYS001
Science and Technology Development Fund, Macau SAR (0117/2019/A3) ; The Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province (2023LSYS001) .
- Language
- English
- Electronic publication date
- 12/30/2025
- Date published
- 02/2026
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9985112975602771
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