Related Experiment Video
Updated: Sep 18, 2025
A Reproducible Intensive Care Unit-Oriented Endotoxin Model in Rats
Published on: February 20, 2021
Establishment of a Novel in vitro Model of Sepsis-Induced Myocardial Injury Using Septic Serum: A Comprehensive
Hang Yang1, Lin Feng2, Zhenjie Jiang1
1Department of Anesthesiology, Anesthesiology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
Insights
The septic serum model provides a more accurate in vitro representation of sepsis-induced myocardial injury compared to lipopolysaccharide or tumor necrosis factor-α models. This finding aids in understanding sepsis pathophysiology and developing targeted therapies for heart damage.
Area of Science:
- Cardiology
- Pathophysiology
- Molecular Biology
Background:
- Sepsis is a critical condition where myocardial injury significantly impacts patient outcomes.
- The exact mechanisms of sepsis-induced heart damage are not fully understood.
- Optimal in vitro models for studying sepsis-related cardiac dysfunction are needed.
Purpose of the Study:
- To systematically compare different in vitro models for studying sepsis-induced myocardial injury.
- To identify the most suitable model that reflects the complex pathophysiology of cardiac dysfunction in sepsis.
Main Methods:
- AC16 cardiomyocytes were exposed to lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), or septic serum.
- Evaluated cell viability, cytotoxicity, inflammation, oxidative stress, apoptosis, and cardiac injury biomarkers.
- Analyzed mRNA expression profiles for differentially expressed genes (DEGs) and performed functional enrichment.
- Assessed diagnostic utility using receiver operating characteristic (ROC) analysis.
Main Results:
- Septic serum exposure induced more significant inflammatory responses, oxidative stress, apoptosis, and myocardial damage than LPS or TNF-α.
- Transcriptomic analysis revealed more DEGs (706) in the septic serum model compared to LPS (262) or TNF-α (237).
- The septic serum model demonstrated higher diagnostic accuracy (AUC=0.671, 0.610) for septic cardiomyopathy datasets.
Conclusions:
- Septic serum serves as a superior in vitro model for sepsis-induced myocardial injury.
- This model offers a physiologically relevant platform for investigating sepsis-related cardiac pathophysiology.
- The findings facilitate a deeper understanding of the complex mechanisms involved in sepsis-induced heart damage.
Background:
Sepsis is a life-threatening systemic inflammatory syndrome, in which myocardial injury plays a key role in disease progression and poor outcomes. However, the precise mechanisms underlying sepsis-induced myocardial injury remain unclear, and the most appropriate in vitro model for its investigation remains to be established. This study aimed to systematically compare different in vitro models to determine the most appropriate model for studying the pathophysiological mechanisms of sepsis-induced myocardial injury.
Materials And Methods:
AC16 cardiomyocytes were treated with lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), or septic serum for 24 hours to induce myocardial injury. Cell viability, cytotoxicity, inflammatory response, oxidative stress, apoptosis, and myocardial injury biomarkers were assessed to evaluate model performance. The mRNA expression profiles were analyzed to identify differentially expressed genes (DEGs), followed by functional enrichment analysis. The diagnostic utility of each model was assessed using receiver operating characteristic (ROC) analysis.
Results:
While LPS and TNF-α-treated cardiomyocytes exhibited similar injury features, both only partially captured the complexity of the sepsis-induced myocardial injury phenotype. In contrast, cardiomyocytes exposed to septic serum demonstrated more pronounced inflammatory responses, oxidative stress, apoptosis, and myocardial damage. Transcriptomic analysis revealed that the septic serum model induced 706 DEGs, significantly more than LPS (262 DEGs) or TNF-α (237 DEGs), and enriched in a broader array of biological processes and signaling pathways. ROC analysis confirmed that the septic serum model (AUC=0.671, 0.610) had higher diagnostic accuracy for septic cardiomyopathy datasets compared to the LPS (AUC= 0.548, 0.426) and TNF-α (AUC= 0.470, 0.559) models.
Conclusion:
This study introduces a novel in vitro approach using septic serum to model sepsis-induced myocardial injury, providing a physiologically relevant platform that more accurately reflects the complex pathophysiology of the disease.
