MiR-1 alleviates chronic heart failure through HCN2/HCN4 axis in vitro

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• MicroRNA Therapeutics

Background:

• Chronic heart failure (CHF) is a complex, progressive cardiovascular condition.
• MicroRNAs (miRNAs) are emerging as critical regulators in cardiac pathophysiology.
• The role of miR-1 in CHF pathogenesis and its specific molecular targets remain incompletely understood.

Purpose of the Study:

• To investigate the regulatory role of miR-1 in chronic heart failure (CHF).
• To elucidate the involvement of hyperpolarization-activated cyclic nucleotide-gated channels 2 and 4 (HCN2/HCN4) in miR-1's effect on CHF.
• To explore the potential of miR-1 as a therapeutic target for CHF.

Main Methods:

• Assessed miR-1 expression and NT-proBNP levels in CHF patients.
• Utilized an in vitro cellular model (H9c2 cells) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R).
• Quantified miR-1, HCN2, HCN4, TNF-α, and IL-6 levels using RT-qPCR, western blot, and ELISA; validated miR-1 targets with dual luciferase assays; assessed cell viability (MTT assay) and apoptosis (flow cytometry).

Main Results:

• miR-1 levels were significantly reduced in CHF patients and OGD/R-treated H9c2 cells.
• Overexpression of miR-1 suppressed TNF-α and IL-6 secretion, enhanced cell viability, and reduced apoptosis in OGD/R-treated cells.
• HCN2 and HCN4 were identified as direct targets of miR-1; their overexpression counteracted miR-1's protective effects, decreasing cell viability and increasing apoptosis.

Conclusions:

• miR-1 directly targets HCN2 and HCN4, regulating cell viability and apoptosis in the context of CHF.
• The miR-1/HCN2/HCN4 axis represents a potential therapeutic strategy for managing chronic heart failure.
• Further research into miR-1 modulation could offer novel treatment avenues for CHF patients.