{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:35:34Z","timestamp":1791851734029,"version":"4.3.4"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in patients with end-stage renal disease, yet its long-term patency is threatened by neointimal hyperplasia (NIH). N\n              <jats:sup>6<\/jats:sup>\n              -methyladenosine (m\n              <jats:sup>6<\/jats:sup>\n              A), a prevalent RNA modification catalyzed by METTL3 (methyltransferase-like 3), plays a regulatory role in cardiovascular remodeling. Our previous studies found that N\n              <jats:sup>6<\/jats:sup>\n              -methyladenosine methyltransferase METTL3 mediated cardiomyocyte proliferation and heart repair after myocardial ischemia. However, its impact on AVF-related NIH remains unclear.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We examined m\n              <jats:sup>6<\/jats:sup>\n              A levels and METTL3 expression in human and murine AVF tissues. Using smooth muscle cell\u2013specific METTL3 conditional knockout and METTL3-overexpressing (adeno-associated virus\u2013METTL3) mouse models, we evaluated NIH formation. In vitro, we analyzed vascular smooth muscle cell proliferation, migration, phenotypic switching, and ferroptosis. m\n              <jats:sup>6<\/jats:sup>\n              A epitranscriptomic microarray and RNA stability assays were used to explore downstream targets and mechanisms.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              METTL3 was significantly upregulated in AVF tissues and vascular smooth muscle cells undergoing dedifferentiation. METTL3 deletion attenuated, while overexpression exacerbated, NIH in vivo. METTL3 enhanced vascular smooth muscle cell proliferation, migration, and phenotypic switching, while suppressing ferroptosis. Mechanistically, METTL3 increased m\n              <jats:sup>6<\/jats:sup>\n              A modification of SLC7A11 (solute carrier family 7 member 11) mRNA, stabilized its transcript, and promoted translation via recruitment of the m\n              <jats:sup>6<\/jats:sup>\n              A reader YTHDF1 (YTH [YT521-B homology domain] N6-methyladenosine RNA-binding protein 1). Silencing SLC7A11 or YTHDF1 abrogated METTL3-induced phenotypic changes and ferroptosis resistance.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>The METTL3-YTHDF1-SLC7A11 axis facilitates AVF NIH by regulating vascular smooth muscle cell dedifferentiation and ferroptosis. These findings uncover a novel epitranscriptional mechanism and suggest a potential therapeutic target for AVF stenosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321014","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T09:01:00Z","timestamp":1747904460000},"page":"1124-1144","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["METTL3-Mediated m\n            <sup>6<\/sup>\n            A mRNA Modification Facilitates Neointimal Hyperplasia in Arteriovenous Fistula"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8333-6348","authenticated-orcid":true,"given":"Yao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, China (Y.Z., Z.L., H.M., C.Z., J.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4848-0798","authenticated-orcid":true,"given":"Zhaozheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, China (Y.Z., Z.L., H.M., C.Z., J.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4405-0471","authenticated-orcid":true,"given":"Huimin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, China (Y.Z., Z.L., H.M., C.Z., J.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1011-0954","authenticated-orcid":true,"given":"Zhenwei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy at The Second Affiliated Hospital, and Department of Pharmacology (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education) at College of Pharmacy (Z.P., B.C.), Harbin Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-867X","authenticated-orcid":true,"given":"Benzhi","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy at The Second Affiliated Hospital, and Department of Pharmacology (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education) at College of Pharmacy (Z.P., B.C.), Harbin Medical University, China."},{"name":"Department of Clinical Pharmacology (the Heilongjiang Key Laboratory of Drug Research) (B.C.), Harbin Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2110-5501","authenticated-orcid":true,"given":"Chengwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second 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