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miR-21-3p controls sepsis-associated cardiac dysfunction via regulating SORBS2
Hui Wang1, Yihua Bei2, Shutong Shen1
1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Journal of Molecular and Cellular Cardiology
|April 2, 2016
Summary
MicroRNA-21-3p (miR-21-3p) drives sepsis-induced cardiac dysfunction by targeting SORBS2. Inhibiting miR-21-3p protects heart function and improves survival in sepsis, offering a potential therapeutic strategy.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Sepsis-induced cardiac dysfunction is a leading cause of mortality in intensive care units.
- MicroRNAs (miRNAs) show potential as sepsis biomarkers, but their functional roles in septic cardiomyopathy are unclear.
- Understanding miRNA involvement is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the functional role of miR-21-3p in sepsis-associated cardiac dysfunction.
- To identify the molecular targets and pathways regulated by miR-21-3p in the heart during sepsis.
- To evaluate the therapeutic potential of inhibiting miR-21-3p in a mouse model of sepsis.
Main Methods:
- Lipopolysaccharide (LPS) administration to induce sepsis in C57BL/6 mice.
- Assessment of cardiac function (FS, EF), mitochondrial integrity, and autophagy.
- Microarray analysis and qRT-PCR to quantify miR-21-3p and SORBS2 expression.
- Pharmacological inhibition (antagomiR) and forced expression (agomiR) of miR-21-3p.
- Analysis of plasma miR-21-3p levels in septic patients.
Main Results:
- LPS challenge induced cardiac dysfunction, characterized by reduced FS and EF, mitochondrial damage, and altered autophagy.
- miR-21-3p expression was significantly upregulated in LPS-treated mouse hearts.
- Inhibition of miR-21-3p preserved cardiac function and improved survival, while its overexpression worsened cardiac dysfunction.
- SH3 domain-containing protein 2 (SORBS2) was identified as a direct target of miR-21-3p and its expression was reduced in septic hearts.
- Plasma miR-21-3p levels were significantly elevated in septic patients with cardiac dysfunction and served as a specific predictor (AUC=0.939).
Conclusions:
- miR-21-3p plays a critical role in sepsis-associated cardiac dysfunction by repressing SORBS2.
- Inhibition of miR-21-3p represents a promising therapeutic strategy for sepsis-induced cardiomyopathy.
- Plasma miR-21-3p is a potential non-invasive biomarker for diagnosing cardiac dysfunction in sepsis patients.
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