MicroRNA Regulation in Endothelial Function and Angiogenesis

MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level, exerting widespread control over endothelial cell behaviour and blood vessel formation. In endothelial cells, specific miRNAs—often termed angiomiRs—fine-tune the balance between pro-angiogenic and anti-angiogenic signals by targeting key components of signalling pathways such as VEGF, FGF, angiopoietin/Tie-2 and the PI3K/Akt axis. Through direct repression or stabilisation of mRNA transcripts, miRNAs regulate endothelial proliferation, migration, survival and differentiation, orchestrating sprouting angiogenesis, vessel maturation and barrier function. Crosstalk between endothelial cells and supporting perivascular cells is also governed by miRNA-loaded extracellular vesicles, which facilitate paracrine and autocrine signalling under physiological and pathological conditions. At the vascular front, tip cells lead sprouting vessels under the influence of gradients of vascular growth factors; here, miRNAs adjust the expression of regulators of cytoskeletal dynamics and cell–cell junctions to determine tip cell fate. In the stalk cells that follow, miRNAs coordinate proliferation and lumen formation for vessel stability. Dysregulation of endothelial miRNAs contributes to vascular complications in diabetes, ischaemic disease, tumour growth and age-related disorders, underscoring their potential as biomarkers and therapeutic targets. Advances in delivery systems, including lipid nanoparticles and exosome-based carriers, are bringing miRNA-based vascular therapies closer to clinical application, with an emphasis on precision modulation of endothelial function in diverse disease settings.

Research from Nature Portfolio

Recent studies have elucidated how an elevated expression of p75NTR in endothelial cells under high-glucose conditions triggers NF-κB-mediated transcription of miR-503. This miRNA is selectively packaged into endothelial microparticles and transferred to pericytes, where it downregulates EFNB2 and VEGFA, impairing pericyte migration and proliferation. The consequent reduction in pericyte coverage of capillaries increases vascular permeability and hinders post-ischaemic angiogenesis in diabetic models. These findings reveal a mechanistic link between endothelial miRNA secretion and perivascular cell dysfunction, offering therapeutic angles for microvascular complications in diabetes.

MicroRNA Regulation in Endothelial Function and Angiogenesis publication trend

The graph below shows the total number of articles in microrna regulation in endothelial function and angiogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA (miRNA): Small non-coding RNA molecule (~19–25 nucleotides) that regulates gene expression by base-pairing with target mRNAs to inhibit translation or promote degradation.

Endothelial cell (EC): A specialised cell lining the interior surface of blood vessels, critical for barrier function, angiogenesis and vascular homeostasis.

Angiogenesis: The biological process of new blood vessel formation from pre-existing vasculature, essential for development, wound healing and pathological conditions.

Pericyte: Mural cell associated with the abluminal surface of capillaries and microvessels, providing structural support and regulating endothelial stability and permeability.

Tip cell: Leading endothelial cell at the forefront of a sprouting vessel that navigates angiogenic cues to direct new branch formation.

References

1. p75NTR-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte–endothelial crosstalk in diabetes after limb ischaemia. Nature Communications (2015).
2. miR-1233-3p Inhibits Angiopoietin-1-Induced Endothelial Cell Survival, Migration, and Differentiation. Cells (2025).
3. miR‐221‐3p targets Ang‐2 to inhibit the transformation of HCMECs to tip cells. Journal of Cellular and Molecular Medicine (2023).