{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:03:19Z","timestamp":1790834599543,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100014358","name":"Second Affiliated Hospital of Soochow University","doi-asserted-by":"publisher","award":["SDFEYBS1819"],"award-info":[{"award-number":["SDFEYBS1819"]}],"id":[{"id":"10.13039\/501100014358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014358","name":"Second Affiliated Hospital of Soochow University","doi-asserted-by":"publisher","award":["SYS2019062"],"award-info":[{"award-number":["SYS2019062"]}],"id":[{"id":"10.13039\/501100014358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014358","name":"Second Affiliated Hospital of Soochow University","doi-asserted-by":"publisher","award":["SKJY2021099"],"award-info":[{"award-number":["SKJY2021099"]}],"id":[{"id":"10.13039\/501100014358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901840"],"award-info":[{"award-number":["81901840"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Hyperglycemia has been widely reported to induce vascular senescence. We have previously demonstrated that angiotensin II (Ang II) could promote brain vascular smooth muscle cell (VSMC) senescence, and its type 2 (AT2) receptor deletion could enhance VSMC senescence. Therefore, we examined the possible cross-talk between Ang II and hyperglycemia on VSMC senescence, and the roles of AT2 receptor agonist, compound 21 (C21) on it.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Aortic VSMCs were prepared from adult male mice and stimulated with Ang II and\/or high glucose (Glu) and\/or C21 and\/or an autophagy inhibitor, 3-methyladenine (3-MA), and\/or an autophagy agonist, rapamycin (RAP) for the indicated times. Cellular senescence, oxidative stress, and protein expressions were evaluated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Combination treatment with Ang II and Glu synergistically increased the proportion of VSMC senescent area compared with control group and each treatment alone, which was almost completely attenuated by C21 treatment. Moreover, combination treatment induced significant changes in the levels of superoxide anion, the expressions of p21 and pRb, and the ratio of LC3B II\/I expression, which were also significantly attenuated by C21 treatment. The proportion of VSMC senescent area and the levels of superoxide anion by combination treatment were increased after 3-MA treatment, and the proportion of senescent area and the expressions of p21 and pRb were decreased after RAP treatment, both of which were further attenuated by C21 treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Ang II and hyperglycemia synergistically promoted VSMC senescence, at least partly through the participation by autophagy, oxidative stress, and p21-pRb pathway, which could be inhibited by C21.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpac083","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T15:49:38Z","timestamp":1657122578000},"page":"884-891","source":"Crossref","is-referenced-by-count":13,"title":["AT2 Receptor Stimulation Inhibits Vascular Smooth Muscle Cell Senescence Induced by Angiotensin II and Hyperglycemia"],"prefix":"10.1093","volume":"35","author":[{"given":"Hui-Yu","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Soochow University , Suzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3195-5657","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Soochow University , Suzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Soochow University , Suzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Bo","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Soochow University , Suzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-3257","authenticated-orcid":false,"given":"Bao-Shuai","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University , Suzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"2022100310022146500_CIT0001","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrd.2017.116","article-title":"Senescent cells: an emerging target for diseases of ageing","volume":"16","author":"Childs","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"2022100310022146500_CIT0002","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1161\/CIRCRESAHA.111.261388","article-title":"Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for 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