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Published on: May 16, 2020
MiR-141 attenuates sepsis-induced cardiomyopathy by targeting DAPK1
Bo Song1, Xin-Xiang Wang2, Hai-Yan Yang1
1Department of Emergency, 519688YanTaiShan Hospital, YanTai, China.
Objective:
To discuss the possible effects of microRNA-141 (miR-141) in sepsis-induced cardiomyopathy (SIC) via targeting death-associated protein kinase 1 (DAPK1).
Methods:
An SIC mouse model was constructed by abdominal injection of lipopolysaccharide (LPS) and divided into control, LPS, LPS + pre-miR-141, and LPS + anti-miR-141 groups. Hemodynamic indicators and heart function indexes of mice were detected. ELISA was used to determine the serum levels of inflammatory cytokines, while TUNEL staining to observe the apoptosis of myocardial cells of mice, as well as qRT-PCR and Western blotting to clarify the expression of miR-141 and DAPK1. Lastly, in vitro experiment was also conducted on the primary neonatal rat ventricular cardiomyocytes (NRVCMs) to validate the results.
Results:
Mice in the LPS group, as compared to the control group, had lower left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, and ±dp/dt, but a higher left ventricular end-diastolic pressure, while the serum expression of IL-1β, IL-6, TNF-α, and cTn-T was up-regulated evidently with the increased apoptotic index of myocardial tissues. However, miR-141 and Bcl-2/Bax were down-regulated with elevated DAPK1 and cleaved caspase-3. The above changes were ameliorated in mice from the LPS + pre-miR-141 group relative to the LPS group, while those in the LPS + anti-miR-141 group were further deteriorated. In vitro experiment showed that miR-141 overexpression could reduce the apoptosis of LPS-induced NRVCMs and the levels of inflammatory cytokines with the increased cell viability.
Conclusion:
MiR-141 could decrease inflammatory response and reduce myocardial cell apoptosis by targeting DAPK1, thereby playing the promising protective role in SIC.
Insights
MicroRNA-141 (miR-141) protects against sepsis-induced cardiomyopathy (SIC) by targeting DAPK1, reducing inflammation and myocardial cell apoptosis. This finding offers a promising therapeutic strategy for SIC.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Sepsis Pathophysiology
Background:
- Sepsis-induced cardiomyopathy (SIC) is a severe complication of sepsis.
- MicroRNAs play critical roles in regulating cardiac function and inflammation.
- The specific role of microRNA-141 (miR-141) in SIC remains to be fully elucidated.
Purpose of the Study:
- To investigate the therapeutic potential of miR-141 in sepsis-induced cardiomyopathy (SIC).
- To elucidate the underlying molecular mechanism involving the targeting of death-associated protein kinase 1 (DAPK1) by miR-141.
Main Methods:
- Establishment of a lipopolysaccharide (LPS)-induced SIC mouse model.
- Assessment of cardiac function, hemodynamic parameters, and serum inflammatory cytokines.
- Analysis of myocardial cell apoptosis using TUNEL staining.
- Quantification of miR-141 and DAPK1 expression via qRT-PCR and Western blotting.
- In vitro validation using neonatal rat ventricular cardiomyocytes (NRVCMs).
Main Results:
- LPS exposure significantly impaired cardiac function, increased myocardial apoptosis, and elevated inflammatory markers in mice.
- miR-141 expression was downregulated, while DAPK1 and cleaved caspase-3 were upregulated in SIC mice.
- miR-141 restoration ameliorated cardiac dysfunction and apoptosis, whereas miR-141 inhibition exacerbated these effects.
- In vitro studies confirmed that miR-141 overexpression reduced LPS-induced NRVCM apoptosis and inflammation.
Conclusions:
- MiR-141 exerts a protective effect in SIC by suppressing inflammatory responses and reducing myocardial cell apoptosis.
- Targeting DAPK1 is a key mechanism through which miR-141 mediates its protective role in SIC.
- MiR-141 represents a potential therapeutic target for managing sepsis-induced cardiomyopathy.
