Investigation of crucial genes and mitochondrial function impairment in diabetic cardiomyopathy
Maierhaba Tuersuntuoheti1, Lei Zhou2, Juexing Li1
1Department of Cardiology, Jinshan Hospital, Fudan University, Shanghai, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
Background:
Diabetic cardiomyopathy (DCM) is a special type of cardiovascular disease, termed as a situation of abnormal myocardial structure and function that occurs in diabetic patients. However, the most fundamental mechanisms of DCM have not been fully explicated, and useful targets for the therapeutic strategies still need to be explored.
Methods:
In the present study, we combined bioinformatics analysis and in vitro experiments throughout the process of DCM. Differentially Expressed Genes (DEGs) analysis was performed and the weighted gene co-expression network analysis (WGCNA) was constructed to determine the crucial genes that were tightly connected to DCM. Additionally, Functional enrichment analysis was conducted to define biological pathways. To identify the specific molecular mechanism, the human cardiomyocyte cell line (AC16) was stimulated by high glucose (HG, 50 mM D-glucose) and used to imitate DCM condition. Then, we tentatively examined the effect of high glucose on cardiomyocytes, the expression levels of crucial genes were further validated by in vitro experiments.
Results:
Generally, NPPA, IGFBP5, SERPINE1, and C3 emerged as potential therapeutic targets. Functional enrichment analysis performed by bioinformatics indicated that the pathogenesis of DCM is mainly related to heart muscle contraction and calcium (Ca2+) release activation. In vitro, we discovered that high glucose treatment induced cardiomyocyte injury and exacerbated mitochondrial dysfunction remarkably.
Conclusion:
Our research defined four crucial genes, as well as determined that mitochondrial function impairment compromises calcium homeostasis ultimately resulting in contractile dysfunction is a central contributor to DCM progression. Hopefully, this study will offer more effective biomarkers for DCM diagnosis and treatment.
Insights
Diabetic cardiomyopathy involves impaired heart muscle function due to high glucose. This study identifies four key genes and reveals mitochondrial dysfunction impacting calcium homeostasis as central to disease progression.
Area of Science:
- Cardiovascular Disease Research
- Molecular Biology
- Biomedical Science
Background:
- Diabetic cardiomyopathy (DCM) is characterized by abnormal heart structure and function in diabetic patients.
- The underlying mechanisms of DCM remain incompletely understood, necessitating the identification of novel therapeutic targets.
Purpose of the Study:
- To elucidate the fundamental mechanisms of diabetic cardiomyopathy.
- To identify crucial genes and molecular pathways involved in DCM pathogenesis.
- To explore potential therapeutic targets for DCM.
Main Methods:
- Combined bioinformatics analysis including Differentially Expressed Genes (DEGs) and Weighted Gene Co-expression Network Analysis (WGCNA).
- Functional enrichment analysis to identify biological pathways.
- In vitro experiments using a human cardiomyocyte cell line (AC16) stimulated with high glucose to mimic DCM conditions.
Main Results:
- Identified NPPA, IGFBP5, SERPINE1, and C3 as potential therapeutic targets.
- Bioinformatics analysis indicated DCM pathogenesis is linked to heart muscle contraction and calcium (Ca2+) release.
- High glucose treatment induced cardiomyocyte injury and significant mitochondrial dysfunction in vitro.
Conclusions:
- Mitochondrial dysfunction impairs calcium homeostasis, leading to contractile dysfunction and contributing to DCM progression.
- Four crucial genes were identified as potential biomarkers and therapeutic targets for DCM.
- This research provides insights for improved diagnosis and treatment strategies for diabetic cardiomyopathy.
