{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:40Z","timestamp":1792786000825,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81374009"],"award-info":[{"award-number":["81374009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773720"],"award-info":[{"award-number":["81773720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Municipal Science and Technology","award":["201804010490"],"award-info":[{"award-number":["201804010490"]}]},{"name":"Natural Science Foundation of Xinjiang Uygur Autonomous","award":["2015211C248"],"award-info":[{"award-number":["2015211C248"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Investigate if azilsartan protects against myocardial hypertrophy by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Abdominal aortic constriction (AAC)-induced cardiac hypertrophy in rats was applied. Azilsartan or vehicle was administered daily for 6 weeks in sham or AAC rats. Cardiac morphology and ventricular function were determined. Azilsartan effects upon neonatal rat cardiomyocyte (NRCM) hypertrophy and molecular mechanisms were studied in angiotensin (Ang) II-stimulated NRCMs in vitro. Nrf2-small interfering RNA (siRNA) was used to knockdown Nrf2 expression. Messenger RNA (mRNA)\/protein expression of Kelch-like erythroid cell-derived protein (Keap)1 and Nrf2 and its downstream antioxidant enzymes was determined by real-time reverse transcription\u2013quantitative polymerase chain reaction and western blotting, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Azilsartan treatment ameliorated cardiac hypertrophy\/fibrosis significantly in AAC rats. Azilsartan increased expression of Nrf2 protein but decreased expression of Keap1 protein. Upregulation of protein expression of Nrf2\u2019s downstream antioxidant enzymes by azilsartan treatment was observed. Azilsartan inhibited Ang II-induced NRCM hypertrophy significantly and similar effects on the Keap1\u2013Nrf2 pathway were observed in vivo. Nrf2 knockdown markedly counteracted the beneficial effects of azilsartan on NRCM hypertrophy and the Keap1\u2013Nrf2 pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Azilsartan restrained pressure overload-induced cardiac remodelling by activating the Keap1\u2013Nrf2 pathway and increasing expression of downstream antioxidant enzymes to alleviate oxidative stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgab097","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T07:09:31Z","timestamp":1623740971000},"page":"1715-1725","source":"Crossref","is-referenced-by-count":14,"title":["Azilsartan ameliorates ventricular hypertrophy in rats suffering from pressure overload-induced cardiac hypertrophy by activating the Keap1\u2013Nrf2 signalling pathway"],"prefix":"10.1093","volume":"73","author":[{"given":"Ning","family":"Hou","sequence":"first","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Tungwah Hospital of Sun Yat-sen University , Dongguan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Ying","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Department of Clinical Laboratory, General Hospital of Xinjiang Military Region , Urumqi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan-Jian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia-Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Ai","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]},{"name":"Department of Cardiology, Xiangtan Central Hospital , Xiangtan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Xin","family":"Zhan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Biao","family":"Pan","sequence":"additional","affiliation":[{"name":"Tungwah Hospital of Sun Yat-sen University , Dongguan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-5492","authenticated-orcid":false,"given":"Cheng-Feng","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"2024103012144597100_CIT0001","first-page":"53H","article-title":"Role of the renin-angiotensin system in cardiac hypertrophy","volume-title":"Am J 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