ArticleMolecular therapy. Nucleic acids2017
Inhibition of Mef2a Enhances Neovascularization via Post-transcriptional Regulation of 14q32 MicroRNAs miR-329 and miR-494.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 16 citations in OpenAlex.
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- C/D box snoRNA SNORD113-6/AF357425 plays a dual role in integrin signalling and arterial fibroblast function via pre-mRNA processing and 2'O-ribose methylation.Human molecular genetics · 2022Article
- N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4.International journal of molecular sciences · 2022Article
- Inhibition of microRNA-494-3p activates Wnt signaling and reduces proinflammatory macrophage polarization in atherosclerosis.Molecular therapy. Nucleic acids · 2021Article
- Review
- MicroRNA-411 and Its 5'-IsomiR Have Distinct Targets and Functions and Are Differentially Regulated in the Vasculature under Ischemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Antisense Oligonucleotide Inhibition of MicroRNA-494 Halts Atherosclerotic Plaque Progression and Promotes Plaque Stabilization.Molecular therapy. Nucleic acids · 2019Article
- Proteomics analysis indicated the protein expression pattern related to the development of fetal conotruncal defects.Journal of cellular physiology · 2019Article
- IRF3 and IRF7 mediate neovascularization via inflammatory cytokines.Journal of cellular and molecular medicine · 2019Article
- Posttranscriptional Regulation of 14q32 MicroRNAs by the CIRBP and HADHB during Vascular Regeneration after Ischemia.Molecular therapy. Nucleic acids · 2019Article
- miRMap: Profiling 14q32 microRNA Expression and DNA Methylation Throughout the Human Vasculature.Frontiers in cardiovascular medicine · 2019Article
- Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Improving the efficacy of neovascularization is a promising strategy to restore perfusion of ischemic tissues in patients with peripheral arterial disease. The 14q32 microRNA cluster is highly involved in neovascularization. The Mef2a transcription factor has been shown to induce transcription of the microRNAs within this cluster. We inhibited expression of Mef2a using gene-silencing oligonucleotides (GSOs) in an in vivo hind limb ischemia model. Treatment with GSO-Mef2a clearly improved blood flow recovery within 3 days (44% recovery versus 25% recovery in control) and persisted until 14 days after ischemia induction (80% recovery versus 60% recovery in control). Animals treated with GSO-Mef2a showed increased arteriogenesis and angiogenesis in the relevant muscle tissues. Inhibition of Mef2a decreased expression of 14q32 microRNAs miR-329 (p = 0.026) and miR-494 (trend, p = 0.06), but not of other 14q32 microRNAs, nor of 14q32 microRNA precursors. Because Mef2a did not influence 14q32 microRNA transcription, we hypothesized it functions as an RNA-binding protein that influences processing of 14q32 microRNA miR-329 and miR-494. Mef2A immunoprecipitation followed by RNA isolation and rt/qPCR confirmed direct binding of MEF2A to pri-miR-494, supporting this hypothesis. Our study demonstrates a novel function for Mef2a in post-ischemic neovascularization via post-transcriptional regulation of 14q32 microRNAs miR-329 and miR-494.
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