{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T14:43:33Z","timestamp":1759502613893,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Institute of General Medical Sciences and National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL151536"],"award-info":[{"award-number":["R01HL151536"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Mississippi Medical Center Intramural Research Support Program"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypertension is a major risk factor for heart failure. Acetylation of p53 is known to regulate its activities. We have previously identified that p53 acetylation is required for cardiac remodeling in a mouse model of pressure overload-induced heart failure. Acetylation mutant p53 (p53aceKO) mice have been shown to have the ability to regulate SIRT3 KO-induced cardiac fibrosis. In the present study, we hypothesized that p53aceKO mice would exhibit cardiac protection and blunt cardiac fibrosis when subjected to Ang-II-induced hypertension. Control and p53aceKO mice received either a micro-osmotic pump implant administering Ang-II for 28 days or a sham procedure. Blood pressure was measured weekly, and echocardiography was performed every two weeks. Mice were euthanized and hearts were processed for histological analysis. While both control and p53aceKO mice receiving Ang-II exhibit increased systolic and diastolic blood pressures, control mice also demonstrate increases in ejection fraction and fractional shortening compared to the sham, while p53aceKO mice do not. Furthermore, control mice receiving Ang-II exhibit decreased left ventricular diameter and volume at end-systole and end-diastole, as well as thickening of both the anterior and posterior walls, while p53aceKO mice exhibit no significant changes in any of these parameters. Additionally, p53aceKO mice do not exhibit the Ang-II infusion-induced cardiac fibrosis seen in control mice treated with Ang-II. Mutation of p53 acetylation is protective against Ang-II infusion-induced cardiac fibrosis and dysfunction in mice. Acetylated p53 may, therefore, be a novel therapeutic target to address complications in the heart associated with hypertension.<\/jats:p>","DOI":"10.3390\/ijms26199668","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T14:18:28Z","timestamp":1759501108000},"page":"9668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutation of p53 Acetylation Protects Against Angiotensin-II-Induced Cardiac Dysfunction and Fibrosis"],"prefix":"10.3390","volume":"26","author":[{"given":"Aubrey C.","family":"Cantrell","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2432-6861","authenticated-orcid":false,"given":"Quinesha A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9203-4336","authenticated-orcid":false,"given":"Jian-Xiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-2807","authenticated-orcid":false,"given":"Heng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/HHF.0b013e318291329a","article-title":"Forecasting the impact of heart failure in the United States: A policy statement from the American Heart Association","volume":"6","author":"Heidenreich","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1001\/jama.1996.03530440037034","article-title":"The progression from hypertension to congestive heart failure","volume":"275","author":"Levy","year":"1996","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/j.1440-1681.2003.03942.x","article-title":"Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling","volume":"30","author":"Zhu","year":"2003","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1161\/01.CIR.101.10.1130","article-title":"Angiotensin II has multiple profibrotic effects in human cardiac fibroblasts","volume":"101","author":"Kawano","year":"2000","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1161\/CIRCRESAHA.121.320324","article-title":"p53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload","volume":"133","author":"Liu","year":"2023","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Peng, T., Liu, M., Hu, L., Guo, D., Wang, D., Qi, B., Ren, G., Hu, C., Zhang, F., and Chun, H.J. (2022). LncRNA Airn alleviates diabetic cardiac fibrosis by inhibiting activation of cardiac fibroblasts via a m6A-IMP2-p53 axis. Biol. Direct, 17.","DOI":"10.1186\/s13062-022-00346-6"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110974","DOI":"10.1016\/j.cellsig.2023.110974","article-title":"PKD knockdown mitigates Ang II-induced cardiac hypertrophy and ferroptosis via the JNK\/P53 signaling pathway","volume":"113","author":"Lv","year":"2024","journal-title":"Cell. Signal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.celrep.2016.09.022","article-title":"Acetylation Is Crucial for p53-Mediated Ferroptosis and Tumor Suppression","volume":"17","author":"Wang","year":"2016","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.cell.2012.04.026","article-title":"Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence","volume":"149","author":"Li","year":"2012","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ye, Z., Xia, Y., Li, L., Li, B., Chen, L., Yu, W., Ruan, Y., Rao, T., Zhou, X., and Cheng, F. (2023). p53 deacetylation alleviates calcium oxalate deposition-induced renal fibrosis by inhibiting ferroptosis. Biomed. Pharmacother., 164.","DOI":"10.1016\/j.biopha.2023.114925"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Su, H., Cantrell, A.C., Chen, J.X., Gu, W., and Zeng, H. (2023). SIRT3 Deficiency Enhances Ferroptosis and Promotes Cardiac Fibrosis via p53 Acetylation. Cells, 12.","DOI":"10.3390\/cells12101428"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1161\/ATVBAHA.123.319601","article-title":"p53 Acetylation Exerts Critical Roles in Pressure Overload-Induced Coronary Microvascular Dysfunction and Heart Failure in Mice","volume":"44","author":"He","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1590\/S0100-879X2007000500018","article-title":"Sex differences in angiotensin II- induced hypertension","volume":"40","author":"Xue","year":"2007","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"He, X., Williams, Q.A., Cantrell, A.C., Besanson, J., Zeng, H., and Chen, J.X. (2024). TIGAR Deficiency Blunts Angiotensin-II-Induced Cardiac Hypertrophy in Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042433"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.yjmcc.2024.05.003","article-title":"Ferrostatin-1 specifically targets mitochondrial iron-sulfur clusters and aconitase to improve cardiac function in Sirtuin 3 cardiomyocyte knockout mice","volume":"192","author":"Cantrell","year":"2024","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.ijcard.2016.04.092","article-title":"Ablation of SIRT3 causes coronary microvascular dysfunction and impairs cardiac recovery post myocardial ischemia","volume":"215","author":"He","year":"2016","journal-title":"Int. J. 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