Related Experiment Video
Updated: Jul 10, 2025
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Sepsis induced cardiotoxicity by promoting cardiomyocyte cuproptosis
Jingru Yan1, Zhangyi Li2, Yilan Li1
1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China.
Insights
Sepsis-induced cardiotoxicity, a major cause of death, is linked to cuproptosis. Key genes like CD274 and VEGFA show altered expression, revealing new molecular mechanisms for this condition.
Area of Science:
- Cardiovascular biology
- Molecular mechanisms of disease
- Sepsis research
Background:
- Sepsis-induced cardiotoxicity is a primary driver of sepsis-related mortality.
- The precise molecular underpinnings of sepsis-induced cardiotoxicity remain largely unknown.
- Identifying these mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To elucidate the key molecular mechanisms driving sepsis-induced cardiotoxicity.
- To investigate the role of cuproptosis and N6-Methyladenosine (m6A) methylation in this condition.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets (GSE63920, GSE44363, GSE159309) for sepsis-induced cardiotoxicity data.
- Performed functional enrichment analysis (GO, KEGG) to identify related signaling pathways.
- Examined the interplay between cuproptosis-related genes (CRGs) and m6A methylation in a mouse model.
Main Results:
- Significantly altered expression of CRGs including CD274, CP, VEGFA, COX11, CCL8, MAP2K1, and AOC3 was observed.
- A significant correlation was found between differentially regulated CRGs and m6A methylation genes.
- Enrichment analysis highlighted pathways involved in immune response and cellular processes.
Conclusions:
- Cuproptosis is strongly associated with the development of sepsis-induced cardiotoxicity.
- Specific genes (CD274, CP, VEGFA, COX11, CCL8, MAP2K1, AOC3) are key players in this process.
- The interplay between CRGs and m6A methylation offers novel insights into sepsis-induced cardiotoxicity mechanisms.
Background:
Currently, sepsis induced cardiotoxicity is among the major causes of sepsis-related death. The specific molecular mechanisms of sepsis induced cardiotoxicity are currently unknown. Therefore, the purpose of this paper is to identify the key molecule mechanisms for sepsis induced cardiotoxicity.
Methods:
Original data of sepsis induced cardiotoxicity was derived from Gene Expression Omnibus (GEO; GSE63920; GSE44363; GSE159309) dataset. Functional enrichment analysis was used to analysis sepsis induced cardiotoxicity related signaling pathways. Our findings also have explored the relationship of cuproptosis and N6-Methyladenosine (m6A) in sepsis induced cardiotoxicity. Mice are randomly assigned to 3 groups: saline treatment control group, LPS group administered a single 5 mg/kg dose of LPS for 24 h, LPS + CD274 inhibitor group administered 10 mg/kg CD274 inhibitor for 24 h.
Results:
Overall, expression of cuproptosis-related genes (CRGs) CD274, Ceruloplasmin (CP), Vascular endothelial growth factor A (VEGFA), Copper chaperone for cytochrome c oxidase 11 (COX11), chemokine C-C motif ligand 8 (CCL8), Mitogen-activated protein kinase kinase 1(MAP2K1), Amine oxidase 3 (AOC3) were significantly altered in sepsis induced cardiotoxicity. The results of spearman correlation analysis was significant relationship between differentially regulated genes (DEGs) of CRGs and the expression level of m6A methylation genes. GO and KEGG showed that these genes were enriched in response to interferon-beta, MHC class I peptide loading complex, proteasome core complex, chemokine receptor binding, TAP binding, chemokine activity, cytokine activity and many more. These findings suggest that cuproptosis is strongly associated with sepsis induced cardiotoxicity.
Conclusion:
In the present study, we found that cuproptosis were associated with sepsis induced cardiotoxicity. The CD274, CP, VEGFA, COX11, CCL8, MAP2K1, AOC3 genes are showing a significant difference expression in sepsis induced cardiotoxicity. Our studies have found significant correlations between CRGs and m6A methylation related genes in sepsis induced cardiotoxicity. These results provide insight into mechanism for sepsis induced cardiotoxicity.
Related Concept Videos
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...