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Published on: June 3, 2018
MicroRNA-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats
Hai-Qiang Sang1, Zheng-Ming Jiang1, Qiu-Ping Zhao2
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, 450052 Henan, Zhengzhou, PR China.
Objective:
MicroRNAs (miRNAs), a group of small non-coding RNAs that fine tune translation of multiple target mRNAs, have been implicated in the development and progression of heart failure.
Methods:
The present study was undertaken to determine the roles of miR-133a on the anatomical, hemodynamic and fibrosis of heart in the chronic heart failure rats, and the downstream signaling pathway.
Results:
The expression of miR-133a in the heart of chronic heart failure from patients or rats was decreased. The miR-133a mimic and miR-133a overexpression caused a decrease in the heart weight/body weight (HW/BW) and LVEDP, and an increase in the LVSP and +LV dP/dt(max) in the chronic heart failure rats. However, the miR-133a inhibitor promoted the HW/BW and LVEDP, and caused a decrease in the LVSP and LV dP/dt(max) in the chronic heart failure rats. The miR-133a mimic and miR-133a overexpression significantly caused a decrease in the fibrosis of heart in chronic heart failure rats. The Akt inhibitor TCN abolished the effects of miR-133a on the HW/BW and LVEDP decrease, LVSP and LV dP/dt(max) increase in the chronic heart failure rats. The miR-133a increased the expression of phosphorylated Akt in the heart of chronic heart failure rats.
Conclusion:
These results demonstrated that miR-133a improves the cardiac function and fibrosis through inhibiting Akt in heart failure rats.
Insights
MicroRNA-133a (miR-133a) levels decrease in heart failure. Restoring miR-133a improves cardiac function and reduces fibrosis by inhibiting the Akt pathway in rat models.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biochemistry
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs crucial for regulating gene expression.
- miRNAs play significant roles in the development and progression of heart failure.
- Dysregulation of specific miRNAs, like miR-133a, is implicated in cardiac pathophysiology.
Purpose of the Study:
- To investigate the functional role of miR-133a in chronic heart failure.
- To elucidate the effects of miR-133a on cardiac anatomy, hemodynamics, and fibrosis.
- To identify the downstream signaling pathway modulated by miR-133a in heart failure.
Main Methods:
- Utilized a rat model of chronic heart failure.
- Administered miR-133a mimics and inhibitors to assess functional changes.
- Measured cardiac parameters including heart weight/body weight ratio, left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), and +LV dP/dt(max).
- Assessed cardiac fibrosis using histological analysis.
- Investigated the involvement of the Akt signaling pathway, including phosphorylation levels and response to Akt inhibitor TCN.
Main Results:
- miR-133a expression was found to be decreased in the hearts of chronic heart failure patients and rats.
- miR-133a restoration (mimic/overexpression) improved cardiac function (increased LVSP and +LV dP/dt(max)) and reduced cardiac fibrosis.
- Inhibition of miR-133a exacerbated heart failure markers (increased HW/BW and LVEDP, decreased LVSP and +LV dP/dt(max)).
- The beneficial effects of miR-133a were associated with increased Akt phosphorylation, and Akt inhibition abolished these effects.
Conclusions:
- miR-133a plays a protective role in chronic heart failure.
- Restoration of miR-133a levels can ameliorate cardiac dysfunction and fibrosis.
- The mechanism involves the inhibition of the Akt signaling pathway.
