{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:05:31Z","timestamp":1784696731279,"version":"3.55.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Myocardial fibrosis (MF) is a pathological process often triggered by chronic inflammation and pressure overload. This study aimed to investigate the therapeutic potential of ranitidine, a histamine H2 receptor antagonist, on MF and explore its underlying mechanisms, focusing on the FAK\/Src pathway and inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A mouse model of MF was established by transverse aortic constriction (TAC). Cardiac function was assessed by echocardiography. Histopathological changes, collagen deposition, mast cell infiltration, and the expression of histamine and its H2 receptor were examined.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , NIH\/3T3 fibroblasts were stimulated with TGF-\u03b21 to induce fibrotic activation. The effects of ranitidine on collagen synthesis, the expression of fibrotic markers (\u03b1-SMA, Collagen I\/III), and the phosphorylation of FAK\/Src were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Findings<\/jats:title>\n                    <jats:p>Ranitidine treatment significantly improved TAC-induced cardiac dysfunction and attenuated myocardial fibrosis, as evidenced by reduced collagen deposition. It also markedly decreased mast cell infiltration and the expression of histamine and H2 receptor in cardiac tissues. In TGF-\u03b21-stimulated fibroblasts, ranitidine dose-dependently reduced collagen synthesis, downregulated \u03b1-SMA, Collagen I, and Collagen III expression, and suppressed the activation of the FAK\/Src pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that ranitidine ameliorates pressure overload-induced myocardial fibrosis, likely in association with attenuation of histamine\/H2 receptor-related inflammatory responses and reduced FAK\/Src activation. This study suggests the repurposing potential of ranitidine for treating MF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1874499","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:45:16Z","timestamp":1784695516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ranitidine attenuates myocardial fibrosis by suppressing histamine\/H2 receptor signaling and FAK\/Src activation"],"prefix":"10.3389","volume":"17","author":[{"given":"Liwen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiexin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]},{"name":"Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghe","family":"Hu","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The General Hospital of Western Theater Command","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Affiliated Hospital of Southwest Jiaotong University\/The Third People\u2019s Hospital of Chengdu","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","first-page":"509","article-title":"Histamine and collagen synthesis in keloid and hypertrophic scar","volume":"23","author":"Cohen","year":"1972","journal-title":"Surg. 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