VAMP3 and SNAP23 mediate the disturbed flow-induced endothelial microRNA secretion and smooth muscle hyperplasia
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), increases the endothelial secretion of nonmembrane-bound miR-126-3p and other microRNAs (miRNAs) via the activation of SNAREs, vesicle-associated membrane protein 3 (VAMP3) and synaptosomal-associated protein 23 (SNAP23). Knockdown of VAMP3 and SNAP23 reduces endothelial secretion of miR-126-3p and miR-200a-3p, as well as the proliferation, migration, and suppression of contractile markers in SMCs caused by EC-coculture. Pharmacological intervention of mammalian target of rapamycin complex 1 in ECs blocks endothelial secretion and EC-to-SMC transfer of miR-126-3p through transcriptional inhibition of VAMP3 and SNAP23. Systemic inhibition of VAMP3 and SNAP23 by rapamycin or periadventitial application of the endocytosis inhibitor dynasore ameliorates the disturbed flow-induced neointimal formation, whereas intraluminal overexpression of SNAP23 aggravates it. Our findings demonstrate the flow-pattern-specificity of SNARE activation and its contribution to the miRNA-mediated EC-SMC communication.
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Atheroprotective laminar shear stress induced the release of vesicle-free miR-126-3p and other miRNAs, as well as AGO2, from endothelial cells by activating VAMP3 and SNAP23.
“Recently, it was demonstrated that atheroprotective laminar shear stress induced the release of vesicle-free miR-126-3p and other miRNAs, as well as AGO2, from endothelial cells by activating vesicle-associated membrane protein 3 (VAMP3) and synaptosomal-associated protein 23 (SNAP23) (130).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [130]
miRNAs secreted from endothelium can regulate the activity of smooth muscle cells.
“This study also showed that miRNAs secreted from endothelium can regulate the activity of smooth muscle cells (130).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [130]
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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00402 · Cited by 5,287 · see citing works
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- Authors
- Zhu, J.-J., Liu, Y.-F., Zhang, Y.-P., Zhao, C.-R., Yao, W.-J., Li, Y.-S., Wang, K.-C., Huang, T.-S., Pang, W., Wang, X.-F., Wang, X., Chien, S., & Zhou, J.
- Affiliations
- Ministry of Education of the People's Republic of China (CN)
- University of California San Diego (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-07-17
- Volume
- 114
- Issue
- 31
- Pages
- 8271-8276
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5547597
- OpenAlex
- W2734836859
- Cited by
- 56
- References
- 36
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 4 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 2
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Natural Science Foundation of China (91539116, 31522022, 81470590)
- HHS | National Institutes of Health (HL106579, HL108735)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- VAMP3, SNAP23, SNARE proteins, microRNA secretion, miR-126-3p, miR-200a-3p, flow disturbance, smooth muscle hyperplasia, neointima formation, mTORC1, dynamin, endothelial cell proliferation and migration
- MeSH terms
- Animals, Humans, Hyperplasia, Muscle, Smooth, Vascular, Mice, Knockout, Myocytes, Smooth Muscle, MicroRNAs, Endothelial Cells, SNARE Proteins, Qb-SNARE Proteins, Qc-SNARE Proteins, Vesicle-Associated Membrane Protein 3, Mice
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