ESC Congress 2026 Abstract · Oct 26, 2026
An age-associated microRNA regulates angiogenic capacity and inflammatory signaling in endothelial senescence
By Kalies K, Kaschke L, Wedler L et al.
Ageing is a major driver of vascular alterations, with senescent endothelial and smooth muscle cells contributing to endothelial dysfunction and the development of cardiovascular disease (CVD). MicroRNAs are critical regulators of both CVD and cellular senescence. The expression of microRNA-Y was assessed in non-senescent and replicative senescent human coronary artery endothelial cells (HCAEC) using qRT-PCR. To investigate its functional role in cellular processes and senescence, miR-Y was inhibited using a locked nucleic acid (LNA)-based inhibitor. In silico–predicted targets were validated at both mRNA and protein levels. A machine learning–based analysis of more than 1,200 miRNA datasets comprising 1,800 distinct miRNAs from tissue samples of individuals aged 20 to 90 years identified miR-Y as a key age-associated miRNA. It was significantly upregulated in aged individuals, exhibited high network centrality, and was predicted to regulate over 80% of age-related target genes. In vitro, miR-Y expression was significantly increased in replicative senescent compared to non-senescent HCAEC (p<0.05), as well as in aortic endothelial cells from old versus young mice. Transfection with an LNA inhibitor effectively reduced miR-Y levels. Functional assays demonstrated that miR-Y inhibition enhanced angiogenic capacity in both non-senescent and replicative senescent HCAEC, as evidenced by tube formation and sprouting assays (p<0.05). However, inhibition also increased cell death in non-senescent cells (p<0.05) and was associated with enlarged nuclear size. In senescent HCAEC, miR-Y inhibition led to elevated expression of the pro-inflammatory cytokines TNF-α (p<0.01), IL-1β (p<0.05), and IL-6 (p<0.05). In summary, inhibition of miR-Y improved angiogenic capacities in non-senescent and replicative senescent HCAEC, indicating a positive effect on vascular regeneration. However, its role in cellular senescence remains inconclusive and needs further evaluation. In conclusion, inhibition of miR-Y improves angiogenic capacity in both non-senescent and replicative senescent endothelial cells, suggesting a potential role in promoting vascular regeneration. However, its impact on cellular senescence and inflammatory signaling appears complex and warrants further investigation.