miR-486-3p ameliorates aging-related impaired angiogenesis in adult moyamoya disease by targeting Forkhead Box O4

Chen, J., Wen, Y., Chen, S., Long, T., Chen, F., Wang, Z., Zhang, G.-Z., Li, M., Zhang, S., Kang, H., Feng, W., Wang, G.

Nanfang Hospital of Southern Medical UniversityNanfang Hospital of Southern Medical University · biorxiv

Paper

Abstract

Objective: Investigate miR-486-3p's role in alleviating age-related angiogenic decline in Moyamoya disease (MMD) by regulating senescent endothelial cells. Methods: Clinical analysis of 151 MMD patients correlated age with postoperative angiogenesis (DSA grading). Senescent HUVECs (SA-{beta}-gal>80%) exhibited elevated SASP factors (IL-6/IL-8/MCP-1). Functional assays (EdU/Transwell/Matrigel) and bioinformatics identified miR-486-3p targets, validated via luciferase/Western blot. Results: Patients [≥]35 years had 3.67-fold higher risk of poor angiogenesis (OR=3.67). Senescent HUVECs showed 10-16-fold higher SASP secretion (p<0.01). miR-486-3p overexpression increased proliferation (EdU+25%), migration (1.7-fold), and tube formation (+40% branches) in senescent cells (p<0.01) and enhanced angiogenesis in vivo (p<0.001). miR-486-3p directly targeted FOXO4, reducing its luciferase activity (-35%) and protein levels (-37%) (p<0.01), suppressing SASP. Conclusion: miR-486-3p enhances post-revascularization angiogenesis in MMD by inhibiting FOXO4-mediated SASP, offering a therapeutic target and predictive biomarker.

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Research summary

miR-486-3p enhances angiogenesis in moyamoya disease by targeting FOXO4 to suppress senescence-associated secretory phenotype (SASP). The paper addresses a mechanism related to aging by targeting cellular senescence, which is a key factor in age-related decline in tissue regeneration and function.

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