{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:43Z","timestamp":1786566523320,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aimed at investigating whether Angiotensin\u2010(1\u20107) [Ang\u2010(1\u20107)] could alleviate cardiac fibrosis by modulating the expression of Rac1 and Rad GTPase and evaluating the specific mechanism in rat cardiac fibroblasts (CFs) and in canine atrial rapid pacing models. Fresh CFs were isolated from ventricles of 1\u2009~\u20093 day\u2010old Sprague\u2010Dawley rats, and were randomly divided into control group, LPS group, Ang\u2010(1\u20107) group and LPS+Ang\u2010(1\u20107) group. CCK8 was used to detect cell proliferation. qRT\u2010PCR was to detect the mRNA expression of ACE2. Mongrel dogs were randomized into four groups: Sham\u2010operated (Sham), AF\u2010Control, AF\u2010EGFP and AF\u2010ACE2 groups. Immunoperoxidase staining was used to test Rac1 and Gem expression. Collagen fibers in heart were stained a red color and extent of cardiac fibrosis was evaluated. Histopathology was to observe actin,\u03b1\u2010smooth. Enzyme\u2010Linked Immunosorbent Assay was to detect Ang II and Ang\u2010(1\u20107) expression in canine atrial tissue. And western blot analysis was to detect the protein expression of iNOS, COX2, \u03b1\u2010SMA, Rac1, ACE, and AT1R in cells and tissues. Cellular experiments showed LPS promoted proliferation of fibroblasts, which could be inhibited by Ang\u2010(1\u20107) (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05). Compared with control group, LPS\u2010induced CFs showed a significant increase in protein expression of iNOS, COX2, and \u03b1\u2010SMA, which promoted cell proliferation. However, the application of Ang\u2010(1\u20107) reversed these effects and suppressed the ACE\/AT1R signaling pathway in LPS\u2010induced CFs. In animal experiments, ACE2 over\u2010expression would up\u2010regulate atrial Ang\u2010(1\u20107) and AT2R and reduce atrial angiotensin II (Ang II) and AT1R expressions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In AF\u2010ACE2 group, Rac1 was down\u2010regulated and Rad GTPase was up\u2010regulated, in comparison with AF\u2010Control and AF\u2010EGFP groups, associated with reductions of CTGF, fibrosis\u2010related factors \u03b1\u2010SMA and N\u2010cadherin. ACE2 was found to alleviate cardiac fibrosis through the Ang(1\u20107)\/Mas signaling pathway in animal experiments.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70814","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:15:39Z","timestamp":1775816139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ACE2 Mediated Cardiac Fibrosis Alleviation Through Angiotensin\u2010(1\u20107)\/Mas Axis Regulation of the Renin\u2010Angiotensin System\/Rac Signaling Pathway"],"prefix":"10.1002","volume":"40","author":[{"given":"Lili","family":"Zou","sequence":"first","affiliation":[{"name":"The Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqi","family":"Fan","sequence":"additional","affiliation":[{"name":"The Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Chen","sequence":"additional","affiliation":[{"name":"The Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1138-9528","authenticated-orcid":false,"given":"Zhiyu","family":"Ling","sequence":"additional","affiliation":[{"name":"The Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Yin","sequence":"additional","affiliation":[{"name":"The Department of Cardiology the Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00504-1"},{"issue":"1","key":"e_1_2_13_3_1","first-page":"53","article-title":"Remodelage Auriculaire, Hypertension Art\u00e9rielle Et Risque C\u00e9r\u00e9bral [Atrial Remodeling, Systemic Hypertension, Stroke]","volume":"98","author":"Donal E.","year":"2005","journal-title":"Archives des Maladies du Coeur et des Vaisseux"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1327839"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6848"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2021.170670"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00023.2016"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01375.x"},{"issue":"11","key":"e_1_2_13_9_1","first-page":"933","article-title":"Research Progress on Influencing Factors of Exercise Capacity of Hypertrophic Obstructive Cardiomyopathy","volume":"40","author":"Yiming Y.","year":"2024","journal-title":"Journal of Clinical Cardiology"},{"issue":"2","key":"e_1_2_13_10_1","first-page":"161","article-title":"Effect of Keli Dazao Xiefei Decoction on Ventricular Remodeling in Rats With Heart Failure After Myocardial Infarction Through ACE2\u2010Ang\u2010(1\u20107)\u2010Mas Axis","volume":"34","author":"Yuan Z. 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