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MiR-148a-3p/SIRT7 Axis Relieves Inflammatory-Induced Endothelial Dysfunction.

Camilla AnastasioIsabella DonisiAntonino CollocaNunzia D'OnofrioMaria Luisa Balestrieri
Published in: International journal of molecular sciences (2024)
In endothelial cells, miR-148a-3p is involved in several pathological pathways, including chronic inflammatory conditions. However, the molecular mechanism of miR-148a-3p in endothelial inflammatory states is, to date, not fully elucidated. To this end, we investigated the involvement of miR-148a-3p in mitochondrial dysfunction and cell death pathways in human aortic endothelial cells (teloHAECs) treated with interleukin-6 (IL-6), a major driver of vascular dysfunction. The results showed that during IL6-activated inflammatory pathways, including increased protein levels of sirtuin 7 (SIRT7) ( p < 0.01), mitochondrial stress ( p < 0.001), and apoptosis ( p < 0.01), a decreased expression of miR-148a-3p was observed ( p < 0.01). The employment of a miR-148a mimic counteracted the IL-6-induced cytokine release ( p < 0.01) and apoptotic cell death ( p < 0.01), and ameliorated mitochondria redox homeostasis and respiration ( p < 0.01). The targeted relationship between miR-148a-3p and SIRT7 was predicted by a bioinformatics database analysis and validated via the dual-luciferase reporter assay. Mechanistically, miR-148a-3p targets the 3' untranslated regions of SIRT7 mRNA, downregulating its expression ( p < 0.01). Herein, these in vitro results support the role of the miR-148a-3p/SIRT7 axis in counteracting mitochondrial damage and apoptosis during endothelial inflammation, unveiling a novel target for future strategies to prevent endothelial dysfunction.
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