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image of LncRNA HULC/miR-556-5p Axis Attenuates Ang II-Induced Cardiac Microvascular Endothelial Cell Dysfunction by Suppressing the AMPK/FOXO3 Pathway

Abstract

Introduction

This study aimed to investigate the regulatory mechanism of the LncRNA HULC/miR-556-5p axis in endothelial cell injury associated with heart failure and its impact on endothelial cell function. Specifically, we explored how HULC interacts with miR-556-5p to modulate cell survival, apoptosis, inflammation, and autophagy in response to Ang II-induced injury.

Methods

Human cardiac microvascular endothelial cells (HCMECs) were utilized as the study model. Ang II-induced HCMEC injury was simulated by treating cells with 100 nM Ang II for 24 hours. The expression levels of HULC, miR-556-5p, and related proteins were assessed using techniques, such as real-time quantitative PCR and Western blot. Cell apoptosis was detected using flow cytometry, and inflammatory cytokine release (TNF-α, IL-1β, and IL-6) was analyzed ELISA. Cell viability was assessed using MTT assays. Immunoblotting was employed to evaluate the phosphorylation status of key signaling molecules, including AMPK and FOXO3.

Results

We observed a crucial role of the LncRNA HULC/miR-556-5p axis in Ang II-induced HCMEC injury. Overexpression of HULC significantly suppressed miR-556-5p activity, thereby reducing cell apoptosis and the release of inflammatory cytokines while promoting cell survival. Further experimental results indicated that miR-556-5p regulated cell function by reducing the expression level of FOXO3 and modulating the AMPK signaling pathway. Additionally, miR-556-5p markedly decreased cellular autophagy levels, further supporting its regulatory role in endothelial cell injury associated with heart failure.

Conclusion

This study elucidates the important role of the LncRNA HULC/miR-556-5p axis in endothelial cell injury associated with heart failure. Our findings provide new insights into the pathophysiological mechanisms of heart failure and highlight the potential therapeutic value of targeting this axis to improve endothelial cell function.

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2026-01-26
2026-01-30

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/content/journals/cmm/10.2174/0115665240395360251112160900
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LncRNA HULC/miR-556-5p Axis Attenuates Ang II-Induced Cardiac Microvascular Endothelial Cell Dysfunction by Suppressing the AMPK/FOXO3 Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0115665240395360251112160900
/content/journals/cmm/10.2174/0115665240395360251112160900
/content/journals/cmm/10.2174/0115665240395360251112160900
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  • Article Type:     Research Article
Keywords: heart failure ; Ang II ; LncRNA HULC ; AMPK ; endothelial cells ; miR-556-5p ; FOXO3

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