{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:12:54Z","timestamp":1790046774169,"version":"4.0.1"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"814","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:p>\n            Hypertension remains a major global health burden with limited effective treatment options. In the present study, the sodium-dependent neutral amino acid transporter SLC38A2 was identified as a regulator of blood pressure (BP) through modulating endothelial nitric oxide (NO) signaling. Here, we show that mice with global and endothelial cell (EC)\u2013specific\n            <jats:italic toggle=\"yes\">Slc38a2<\/jats:italic>\n            gene knockout (\n            <jats:italic toggle=\"yes\">Slc38a2<\/jats:italic>\n            <jats:sup>\u25b3EC<\/jats:sup>\n            ) exhibited reduced blood pressure compared with wild-type controls. Single-cell RNA sequencing analysis revealed enhanced NO biosynthesis in the ECs of the\n            <jats:italic toggle=\"yes\">Slc38a2<\/jats:italic>\n            <jats:sup>\u25b3EC<\/jats:sup>\n            mice. Blockade of endothelial SLC38A2 by its inhibitor methylaminoisobutyric acid (MeAIB) increased NO production through activating the protein kinase B (AKT)\u2013endothelial NO synthase (eNOS) pathway by inhibiting EC uptake of glutamine. Moreover, MeAIB lowered blood pressure in both high-salt and deoxycorticosterone acetate (DOCA)\u2013induced hypertensive mouse and rat models. Last, in two independent population cohorts including a Chinese cohort established by our group and a European cohort from the UK Biobank, the\n            <jats:italic toggle=\"yes\">SLC38A2<\/jats:italic>\n            rs1873793 variant was associated with increased risk of hypertension under a recessive model. Collectively, our findings demonstrate that targeting SLC38A2 may represent a therapeutic target for the treatment of hypertension.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adt5947","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:58:18Z","timestamp":1756922298000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Inhibiting SLC38A2 lowers blood pressure in rodent models of hypertension"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4152-4663","authenticated-orcid":true,"given":"Chunxiu","family":"Du","sequence":"first","affiliation":[{"name":"Wuhu Hospital, East China Normal University, Wuhu, Anhui, 241000, China."},{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-0932","authenticated-orcid":true,"given":"Hu","family":"Xu","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3308-9837","authenticated-orcid":true,"given":"Wenqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5320-0539","authenticated-orcid":true,"given":"Liping","family":"Jiao","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-7868","authenticated-orcid":true,"given":"Yanghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowan","family":"Sun","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6846-5627","authenticated-orcid":true,"given":"Mingxin","family":"Cao","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6289-8758","authenticated-orcid":true,"given":"Yufei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-3954","authenticated-orcid":true,"given":"Yanlin","family":"Guo","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9214-3497","authenticated-orcid":true,"given":"Rongfang","family":"Qiao","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116044, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ye","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Wang","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6108-5738","authenticated-orcid":true,"given":"Lan","family":"Ye","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116044, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6370-1865","authenticated-orcid":true,"given":"Lihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-3980","authenticated-orcid":true,"given":"Dao Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5231-0209","authenticated-orcid":true,"given":"Youfei","family":"Guan","sequence":"additional","affiliation":[{"name":"Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, 116044, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-2423","authenticated-orcid":true,"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuhu Hospital, East China Normal University, Wuhu, Anhui, 241000, China."},{"name":"Health Science Center, East China Normal University, Shanghai, 200241, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00241-0"},{"key":"e_1_3_2_3_2","first-page":"1","article-title":"Hypertension: From basic research to clinical practice","volume":"956","author":"Islam M. S.","year":"2017","unstructured":"M. S. Islam, Hypertension: From basic research to clinical practice. Adv. Exp. Med. Biol. 956, 1\u20132 (2017).","journal-title":"Adv. Exp. Med. Biol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199904223401601"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.06.010"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106931"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/10641963.2017.1416119"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-09107-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12061763"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14132582"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31670-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000133251.40322.20"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-018-0881-z"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11071679"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8607"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.652693"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20180250"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000149748.79945.52"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80647"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038362"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00704-w"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.152587"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198754"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101420"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803180"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32225-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4414\/smw.2010.13122"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.104133"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-003-0007-z"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003301"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.12.033"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15856"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020678"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.07.015"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04417-w"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI179122"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06299-8"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.04.004"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1086\/690236"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11092092"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530245"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101072"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.138505"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902119116"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-021-01252-3"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314172"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.064735"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI145734"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.8.1599"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-6175.2005.04377.x"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adt5947","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:58:22Z","timestamp":1756922302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adt5947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":49,"journal-issue":{"issue":"814","published-print":{"date-parts":[[2025,9,3]]}},"alternative-id":["10.1126\/scitranslmed.adt5947"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adt5947","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"assertion":[{"value":"2024-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-14","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadt5947"}}