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Integrated Omics Insights into Dapagliflozin Effects in Sepsis-Induced Cardiomyopathy
Weiwei Lai1, Li Liu1, Shuhang Wang1
1Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
Insights
Dapagliflozin shows promise in treating sepsis-induced cardiomyopathy (SIC). It reduced adverse cardiovascular events and improved survival in patients and animal models by regulating inflammation and metabolism.
Area of Science:
- Cardiology
- Pharmacology
- Sepsis Research
Background:
- Sepsis-induced cardiomyopathy (SIC) is a critical condition with limited treatments.
- Dapagliflozin, an SGLT2 inhibitor, has known heart benefits but its role in SIC is unproven.
Purpose of the Study:
- To evaluate dapagliflozin's efficacy in sepsis-induced cardiomyopathy.
- To investigate the molecular mechanisms of dapagliflozin in SIC.
Main Methods:
- Retrospective analysis of patients using dapagliflozin for SIC.
- Murine model of SIC (cecal ligation and puncture).
- Multi-omics profiling (transcriptomics, metabolomics) to identify mechanisms.
Main Results:
- Dapagliflozin use reduced major adverse cardiovascular events and improved survival in SIC patients.
- In mice, dapagliflozin improved cardiac function, reduced injury markers, and histological damage.
- Multi-omics revealed dapagliflozin modulates inflammation, enhances autophagy, and regulates metabolic pathways.
Conclusions:
- Dapagliflozin significantly improves cardiac outcomes in SIC.
- It acts by regulating inflammation, metabolism, and cellular survival pathways.
- Dapagliflozin is a potential therapeutic for SIC.
Background:
Sepsis-induced cardiomyopathy (SIC) is a life-threatening cardiac complication of sepsis with limited therapeutic options. Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has demonstrated cardioprotective effects in heart failure, but its role in mitigating sepsis-related cardiac dysfunction remains unclear.
Methods:
A retrospective cohort analysis was conducted to assess the impact of pre-hospital dapagliflozin use on major adverse cardiovascular events (MACEs) and survival in patients with SIC. Additionally, a murine SIC model was established using cecal ligation and puncture (CLP) to evaluate the effects of dapagliflozin on cardiac function, histopathology, and biomarkers of myocardial injury. Transcriptomic and metabolomic profiling, combined with multi-omics integration, was employed to elucidate the molecular mechanisms underlying dapagliflozin's cardioprotective effects.
Results:
In the clinical cohort, pre-hospital dapagliflozin use was associated with a significant reduction in the risk of MACE and improved survival outcomes. In the murine SIC model, dapagliflozin restored cardiac function, reduced biomarkers of myocardial injury, and alleviated histological damage. Multi-omics analysis revealed that dapagliflozin modulates inflammatory responses, enhances autophagy, and regulates metabolic pathways such as AMPK signaling and lipid metabolism. Key regulatory genes and metabolites were identified, providing mechanistic insights into the underlying actions of dapagliflozin.
Conclusions:
Dapagliflozin significantly improves cardiac outcomes in sepsis-induced cardiomyopathy through the multi-level regulation of inflammation, energy metabolism, and cellular survival pathways. These findings establish dapagliflozin as a promising therapeutic strategy for SIC, offering translational insights into the treatment of sepsis-induced cardiac dysfunction.
