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MyD88 is the canonical adaptor of TLRs and IL\u20101Rs, which serves as the central node in regulating inflammatory responses. Previous studies reported the opposite roles of MyD88 in hypertension. In this study, we aimed to determine the role of MyD88 and the underlying mechanisms in hypertension. Cardiomyocyte\u2010specific MyD88 knockout mice, macrophage\u2010specific MyD88 knockout mice, and MyD88 inhibitor\u2010treated mice were challenged with Ang II infusion to establish a cardiac remodelling model. An inflammatory cytokine array was used to determine the internal mediators. Our results showed that cardiomyocyte MyD88 deficiency showed little protection, whereas macrophage MyD88 deficiency and pharmacological MyD88 inhibition using LM8 significantly ameliorated Ang II\u2010induced cardiac inflammation, fibrosis, and dysfunction. The cytokine and chemokine array demonstrated that CXCL1 and CCL2 were differentially expressed between cardiomyocyte\u2010specific MyD88 knockout and macrophage\u2010specific MyD88 knockout mice. Deletion of MyD88 in macrophages significantly decreased macrophage infiltration and suppressed the activation of macrophages, which then reduced the conditioned medium\u2010induced cardiomyocyte hypertrophy. Our study demonstrated that targeting myeloid MyD88 could be a potential strategy in treating hypertensive cardiac remodelling.<\/jats:p>","DOI":"10.1111\/jcmm.70733","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T10:03:50Z","timestamp":1752919430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Myeloid <scp>MyD88<\/scp> Mediates Macrophage Infiltration and Activation in Ang <scp>II<\/scp>\u2010Induced Cardiac Hypertrophy"],"prefix":"10.1111","volume":"29","author":[{"given":"Ke","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Hangzhou Medical College, Zhejiang Provincial People's Hospital Affiliated People's Hospital  Hangzhou Zhejiang China"},{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang 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