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Updated: May 6, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-18a improves human cerebral arteriovenous malformation endothelial cell function
Raquel Ferreira1, Tiago Santos, Arun Amar
1From the Department of Neurological Surgery (R.F., A.A., T.C.C., S.L.G., F.M.H.), Department of Pathology (T.S., T.C.C., F.M.H.), and Department of Molecular Microbiology and Immunology (S.M.T.), Keck School of Medicine, University of Southern California, Los Angeles, CA.
MicroRNA-18a (miR-18a) therapy normalizes brain endothelial cell function in cerebral arteriovenous malformations (AVMs). This microRNA treatment reduces abnormal growth factor production and improves cell structure, offering potential for AVM treatment.
Area of Science:
- Vascular Biology
- Molecular Medicine
- Biotechnology
Background:
- Cerebral arteriovenous malformations (AVMs) are complex vascular diseases characterized by abnormal connections between arteries and veins in the brain.
- Aberrant functions of AVM-derived brain endothelial cells (AVM-BECs) significantly contribute to AVM pathogenesis and associated neurological complications.
- Current therapeutic strategies for AVMs have limitations, necessitating the exploration of novel treatment approaches.
Purpose of the Study:
- To investigate the therapeutic potential of microRNA-18a (miR-18a) in restoring normal function to AVM-BECs.
- To evaluate the effects of miR-18a on key cellular processes in AVM-BECs, including growth factor production, proliferation, and tubule formation.
- To assess the efficacy of miR-18a delivery to AVM-BECs.
Main Methods:
- Human AVM-BECs were cultured and subjected to varying shear flow conditions.
- Quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure mRNA and protein levels of thrombospondin-1, inhibitor of DNA-binding protein 1, VEGF-A, and VEGF-D.
- Cell proliferation was assessed using bromodeoxyuridine incorporation assays, and tubule formation capacity was evaluated using growth factor-reduced Matrigel assays.
Main Results:
- miR-18a treatment upregulated thrombospondin-1 and downregulated inhibitor of DNA-binding protein 1 in AVM-BECs.
- miR-18a significantly reduced the overexpression of VEGF-A and VEGF-D, with VEGF-D overexpression being reported for the first time in AVM.
- These beneficial effects were most pronounced under arterial shear flow conditions, and miR-18a was effectively internalized by AVM-BECs without external transfection agents, leading to reduced proliferation and improved tubule formation.
Conclusions:
- This study demonstrates that miR-18a can effectively induce AVM-BECs towards a more normalized cellular function.
- The findings highlight the novel role of VEGF-D overexpression in AVM pathogenesis.
- MicroRNA-based therapeutics, specifically miR-18a, hold significant clinical promise for the treatment of AVMs and potentially other vascular diseases.
