{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:42:36Z","timestamp":1790606556436,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100459"],"award-info":[{"award-number":["82100459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Education Bureau of Chongqing Government, Chongqing, China","award":["CYB22227"],"award-info":[{"award-number":["CYB22227"]}]},{"DOI":"10.13039\/501100004374","name":"Chongqing Medical University, Chongqing, China","doi-asserted-by":"publisher","award":["W0085"],"award-info":[{"award-number":["W0085"]}],"id":[{"id":"10.13039\/501100004374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Organs modulating blood pressure are associated with a common cytokine known as adipokines. We chose Zinc-alpha2-glycoprotein (ZAG) due to its prioritized transcriptional level in the database. Previous studies showed that ZAG is involved in metabolic disorders. The aim of this study was to investigate its role in hypertension.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Serum ZAG levels were assessed in hypertensive and healthy participants. Blood pressure was monitored in Azgp1\u2212\/\u2212 mice and other animal models by 24-hour ambulatory implanted telemetric transmitters and tail-cuff method. Multi-omics analysis of proteomics and metabolomics were performed to explore possible mechanisms. Serum ZAG levels were significantly decreased and associated with morning urine Na+ excretion in hypertensive participants in a cross-sectional study. This study firstly reported that Azgp1\u2212\/\u2212 mice exhibited increased blood pressure and impaired urinary Na+ excretion, which were restored by AAV9-mediated renal tubule Azgp1 rescue. Azgp1 knockout caused the reprogramming of renal lipid metabolism, and increased Na+\/H+-exchanger (NHE) activity in the renal cortex. Administration with a NHE inhibitor EIPA reversed the impaired urinary Na+ excretion in Azgp1\u2212\/\u2212 mice. Moreover, the activity of carnitine palmitoyltransferase 1 (CPT1), a key enzyme of fatty acid \u03b2-oxidation, was decreased, and the levels of malonyl-CoA, an inhibitor of CPT1, were increased in renal cortex of Azgp1\u2212\/\u2212 mice. Renal Cpt1 rescue improved urinary Na+ excretion and blood pressure in Azgp1\u2212\/\u2212 mice, accompanied by decreased renal fatty acid levels and NHE activity. Finally, administration of recombinant ZAG protein improved blood pressure and urinary Na+ excretion in spontaneous hypertension rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Deficiency of Azgp1 increased the malonyl CoA-mediated inhibition of CPT1 activity, leading to renal lipid metabolism reprogramming, resulting in accumulated fatty acids and increased NHE activity, subsequently decreasing urinary Na+ excretion and causing hypertension. These findings may provide a potential kidney-targeted therapy in the prevention and treatment of hypertension.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae205","type":"journal-article","created":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T13:12:31Z","timestamp":1725801151000},"page":"2134-2146","source":"Crossref","is-referenced-by-count":11,"title":["Zinc-alpha2-glycoprotein modulates blood pressure by regulating renal lipid metabolism reprogramming-mediated urinary Na+ excretion in hypertension"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1652-408X","authenticated-orcid":false,"given":"Xiaoxin","family":"Zhou","sequence":"first","affiliation":[{"name":"Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]},{"name":"Department of Clinical Nutrition, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]},{"name":"Translational Cardiovascular Medicine, Biomedicine Research Center of Strasbourg, UR 3074, University of Strasbourg , 67000 Strasbourg ,","place":["France"]},{"name":"Department of Medical Management, The University Town Hospital of Chongqing Medical University , 401331 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Deng","sequence":"additional","affiliation":[{"name":"Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]},{"name":"Department of Clinical Nutrition, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]},{"name":"Department of Clinical Nutrition, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifu","family":"Lei","sequence":"additional","affiliation":[{"name":"Research Center for Metabolic and Cardiovascular Diseases, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]},{"name":"Department of Clinical Nutrition, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Sciences Research Center, The University Town Hospital of Chongqing Medical University , 401331 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , 400042 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , 400042 Chongqing ,","place":["PR 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,","place":["PR China"]},{"name":"Department of Clinical Nutrition, The Third Affiliated Hospital of Chongqing Medical University , No. 1, Shuanghu Branch Road, Yubei District, 401120 Chongqing ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"2024121420400236000_cvae205-B1","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1001\/jama.2022.19590","article-title":"Treatment of hypertension: a review","volume":"328","author":"Carey","year":"2022","journal-title":"JAMA"},{"key":"2024121420400236000_cvae205-B2","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","article-title":"Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants","volume":"398","author":"NCD Risk Factor Collaboration 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