{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T05:30:33Z","timestamp":1786339833525,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T00:00:00Z","timestamp":1774137600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Angiotensin II (AngII) induces cardiac hypertrophy but the exact mechanism is not known. The present study investigates the role of the interleukin\u20101 receptor\u2010associated kinase (IRAK), in AngII\u2010induced cardiac inflammation, fibrosis and hypertrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J male mice were infused with saline (sham) or AngII (1.5\u00a0mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7day\n                      <jats:sup>\u22121<\/jats:sup>\n                      , subcutaneously) along with vehicle or IRAK\u20101\/4 inhibitor (2.21\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , intra\u2010peritoneal) for 4\u00a0weeks. Cardiac hypertrophy, fibrosis and signalling mechanisms were examined by echocardiography, histopathology, immunohistochemistry, RT\u2010qPCR and immunoblotting, respectively, in the left ventricle (LV). H9C2 cells and primary cardiac fibroblasts were used to complement the in vivo studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>AngII infusion in mice leads to significant alterations in haemodynamic and gravimetric parameters and the development of cardiac hypertrophy, inflammation and fibrosis in comparison with sham mice. Treatment with IRAK\u20101\/4 inhibitor prevented the AngII\u2010induced changes in ejection fraction, fractional shortening, systolic blood pressure and relative heart weight, compared with mice given AngII alone. AngII\u2010induced increase in cardiomyocyte cross\u2010sectional area and fetal genes (Acta1, Mhy6, Nppa) expression were also attenuated in IRAK\u20101\/4 inhibitor\u2010treated mice. CD45, F4\/80, CD68 and CD3 immuno\u2010staining showed reduced immune cell infiltration in IRAK\u20101\/4 inhibitor and AngII\u2010infused mice when compared with AngII alone. IRAK\u20101\/4 inhibitor and siRNA prevented AngII\u2010induced H9C2 cell hypertrophy and activation of fibroblast TGF\u03b2\u2010SMAD pathway, respectively. Mechanistically IRAK\u20101\/4 inhibitor prevents activation of Ang II\u2010induced TLR4\u2010NF\u2010\u03baB and TGF\u03b2\u2010SMAD pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>The IRAK\u20101\/4 inhibitor reduced cardiac inflammation, fibrosis and hypertrophy through the TLR4\u2010NF\u2010\u03baB and TGF\u03b2\u2010SMAD pathways, suggesting therapeutic potential for cardio\u2010inflammatory heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70405","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T04:50:43Z","timestamp":1774241443000},"page":"3409-3423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacological inhibition of the interleukin\u20101 receptor\u2010associated kinase prevents angiotensin II\u2010induced cardiac remodelling in mice"],"prefix":"10.1111","volume":"183","author":[{"given":"Shreya","family":"Jaiswal","sequence":"first","affiliation":[{"name":"Pharmacology Division Council of Scientific and Industrial Research\u2010Central Drug Research Institute (CSIR\u2010CDRI)  Lucknow India"},{"name":"Jawaharlal Nehru University (JNU)  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Sharma","sequence":"additional","affiliation":[{"name":"Pharmacology Division Council of Scientific and Industrial Research\u2010Central Drug Research Institute (CSIR\u2010CDRI)  Lucknow India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-482X","authenticated-orcid":false,"given":"Manoj Kumar","family":"Barthwal","sequence":"additional","affiliation":[{"name":"Pharmacology Division Council of Scientific and 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