Related Experiment Video
Updated: Jul 21, 2025
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Comparative Analysis of Whole Transcriptome Profiles in Septic Cardiomyopathy: Insights from CLP- and LPS-Induced
Karim Ullah1, Yan Li2, Qiaoshan Lin2
1Section of Cardiology, Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, USA.
Insights
This study compared two sepsis models, revealing shared and distinct molecular pathways in septic cardiomyopathy. Findings advance understanding of heart dysfunction in sepsis for better treatment strategies.
Area of Science:
- Cardiology
- Molecular Biology
- Genomics
Background:
- Sepsis causes life-threatening organ dysfunction, with septic cardiomyopathy (SICM) a severe complication.
- Molecular mechanisms of SICM are not fully understood, hindering effective treatment.
- Comparative transcriptomic analysis is crucial for elucidating SICM pathogenesis.
Purpose of the Study:
- To compare whole transcriptome profiles in two mouse models of septic cardiomyopathy.
- To identify shared and distinct molecular pathways in sepsis-induced heart dysfunction.
- To provide insights into molecular mechanisms for developing targeted SICM therapies.
Main Methods:
- Whole transcriptome RNA sequencing in mouse hearts from cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) models.
- Sham-operated mice used as controls for both septic models.
- Comparative analysis of differentially expressed genes (DEGs) and regulatory regions.
Main Results:
- Both CLP and LPS models induced septic heart dysfunction within 24 hours.
- Common transcriptional regulators (Nfkb1, Sp1, Jun) and pathways (inflammation, ROS, JAK-STAT) were identified.
- Distinct transcriptomic profiles suggest model-specific contributions to heart failure.
Conclusions:
- Comparative transcriptomics reveals conserved and unique molecular underpinnings of septic cardiomyopathy.
- Understanding these pathways is vital for personalized treatment strategies for SICM.
- This study provides a foundation for further research into sepsis-induced heart dysfunction.
Abstract:
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles using RNA sequencing in mouse hearts in two widely used mouse models of septic cardiomyopathy. CLP-induced sepsis was achieved by surgical cecal ligation and puncture, while LPS-induced sepsis was induced using a 5 mg/kg intraperitoneal (IP) injection of lipopolysaccharide (LPS). For consistency, we utilized sham-operated mice as the control for septic models. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings demonstrated that both the CLP and lipopolysaccharide LPS methods could induce septic heart dysfunction within 24 h. We identified common transcriptional regulatory regions in the septic hearts of both models, such as Nfkb1, Sp1, and Jun. Moreover, differentially expressed genes (DEGs) in comparison to control were involved in shared pathways, including regulation of inflammatory response, regulation of reactive oxygen species metabolic process, and the JAK-STAT signaling pathway. However, each model presented distinctive whole transcriptome expression profiles and potentially diverse pathways contributing to sepsis-induced heart failure. This extensive comparison enhances our understanding of the molecular basis of septic cardiomyopathy, providing invaluable insights. Accordingly, our study also contributes to the pursuit of effective and personalized treatment strategies for SICM, highlighting the importance of considering the specific causative factors.
