miR‑141 impairs mitochondrial function in cardiomyocytes subjected to hypoxia/reoxygenation by targeting Sirt1 and...

Area of Science:

• Cardiovascular Biology
• Mitochondrial Medicine
• Molecular Cardiology

Background:

• Ischemia/reperfusion (I/R) injury is a significant cause of heart damage.
• Mitochondrial oxidative stress and dysfunction are key pathological features of I/R.
• MicroRNA-141 (miR-141) is linked to mitochondrial dysfunction in oxidant stress models.

Purpose of the Study:

• To investigate the role of miR-141 in cardiomyocyte injury during simulated I/R.
• To determine if miR-141 directly impacts mitochondrial function and viability in cardiomyocytes.

Main Methods:

• HL-1 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to simulate I/R.
• miR-141 expression, cell viability, and mitochondrial function (superoxide production, oxygen utilization, membrane potential) were assessed.
• miR-141 inhibitor and mimic were used to modulate miR-141 levels.
• Luciferase reporter assays, RT-qPCR, and Western blot identified miR-141 targets.

Main Results:

• H/R reduced cardiomyocyte viability and increased miR-141 expression.
• miR-141 inhibition mitigated H/R-induced injury and mitochondrial dysfunction.
• miR-141 mimic exacerbated H/R-induced injury and mitochondrial dysfunction.
• Sirtuin-1 (Sirt1) and Mitofusin-2 (MFN2) were identified as direct targets of miR-141.
• Sirt1 silencing mimicked the effects of miR-141 on MFN2 and mitochondrial function.

Conclusions:

• miR-141 acts as a detrimental factor in I/R-induced cardiomyocyte injury.
• miR-141 promotes injury by targeting Sirt1 and MFN2, leading to mitochondrial dysfunction.
• Targeting miR-141 may offer a therapeutic strategy for I/R cardiac injury.