{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:46:18Z","timestamp":1791830778375,"version":"4.3.4"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>\n                      Hypertension is a major risk factor for cardiovascular diseases. RNA N6-methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) modification is closely linked to hypertension pathogenesis, but key m\n                      <jats:sup>6<\/jats:sup>\n                      A-related factors that regulate blood pressure remain unclear. This study aims to identify these regulators and evaluate their therapeutic potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We assessed RNA m\n                      <jats:sup>6<\/jats:sup>\n                      A changes and METTL (methyltransferase-like) expression in hypertensive aortas via methylated RNA immunoprecipitation sequencing and RNA sequencing (RNA-seq). Global\n                      <jats:italic toggle=\"yes\">Mettl7b<\/jats:italic>\n                      knockout mice and vascular smooth muscle cell (VSMC)\u2013specific\n                      <jats:italic toggle=\"yes\">Mettl7b<\/jats:italic>\n                      knockin and knockout mice were used to evaluate its in vivo role. Downstream target genes were identified via methylated RNA immunoprecipitation sequencing, enhanced cross-linking and immunoprecipitation sequencing, and RNA-seq. METTL7B activators were screened using molecular docking and surface plasmon resonance and validated in vivo via intraperitoneal injection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Under hypertensive stress, METTL7B expression positively correlated with global RNA m\n                      <jats:sup>6<\/jats:sup>\n                      A content, exhibiting concurrent depletion in VSMCs. In vitro biochemical assays revealed that recombinant METTL7B significantly increased RNA m\n                      <jats:sup>6<\/jats:sup>\n                      A levels. Crucially, METTL7B overexpression in METTL3 knockout cells robustly upregulated m\n                      <jats:sup>6<\/jats:sup>\n                      A levels, definitively establishing METTL7B as a novel, METTL3-independent RNA m\n                      <jats:sup>6<\/jats:sup>\n                      A methyltransferase. Physiologically, VSMC-specific Mettl7b ablation exacerbated angiotensin II\u2013induced hypertensive pathogenesis, structural arterial remodeling, and vascular tone, whereas its overexpression exerted potent vasoprotective effects. Mechanistically, METTL7B recruited HNRNPH1 to catalyze m\n                      <jats:sup>6<\/jats:sup>\n                      A deposition at the 3\u2032 untranslated region of FILIP1L mRNA, facilitating its maturation. Importantly, the expression of FILIP1L was positively correlated with blood pressure reduction in humans and mice. Elevated FILIP1L downregulated the expression of its binding protein FLNA (Filamin A), reducing F-actin polymerization, attenuating VSMC contractility, and ultimately lowering blood pressure. Furthermore, FILIP1L overexpression reversed the detrimental effects of\n                      <jats:italic toggle=\"yes\">Mettl7b<\/jats:italic>\n                      knockout on hypertension and vascular remodeling, whereas these effects were not rescued by the mutation of FILIP1L\u2019s m\n                      <jats:sup>6<\/jats:sup>\n                      A site. Elucidating the upstream pathology, we found that stress-induced KLF4 directly bound the METTL7B promoter, transcriptionally repressing its expression. Finally, the Food and Drug Administration\u2013approved drug netarsudil exerted preventive and therapeutic effects on hypertension and vascular remodeling by activating METTL7B; notably, these therapeutic benefits were completely abolished in VSMC-specific\n                      <jats:italic toggle=\"yes\">Mettl7b<\/jats:italic>\n                      knockout mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      Collectively, our study identifies a novel RNA m\n                      <jats:sup>6<\/jats:sup>\n                      A methyltransferase, METTL7B. The METTL7B-HNRNPH1-FILIP1L axis mitigates hypertension by regulating VSMC dedifferentiation and vascular tone. Targeted activation of METTL7B may emerge as a promising strategy for hypertension.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.079407","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:02:55Z","timestamp":1787648575000},"page":"1473-1493","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["METTL7B Mitigates Hypertension and Vascular Remodeling"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-3997","authenticated-orcid":true,"given":"Zhenzhen","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. Cai)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1500-9265","authenticated-orcid":true,"given":"Haizeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. Cai)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-7332","authenticated-orcid":true,"given":"Qiaoxi","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. Cai)."},{"name":"State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Q.Y., X.D., B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyun","family":"Fan","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. Cai)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5538-1774","authenticated-orcid":true,"given":"Xilan","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Q.Y., X.D., B.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4812-3934","authenticated-orcid":true,"given":"Qianhui","family":"Ling","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. Cai)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9709-936X","authenticated-orcid":true,"given":"Xinru","family":"Guo","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. Cai)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0294-5737","authenticated-orcid":true,"given":"Fengkai","family":"Yue","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing, China (Z.C., H.Z., Q.Y., L.F., Q.L., X.G., F.Y., J. Cui, Y.T., J. 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