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Icosapent ethyl activates GPR120 to improve post-myocardial infarction cardiac remodeling by suppressing CXCR3+ inflammatory cells.

Created on 22 Aug 2026

Authors

Lu Liu, Wenhui Niu, Yumeng Jia, Qun Zhang, Tangyu Dai, Dingwei Li, Shuang Song, Yan Ma, Jingjing Wang, Huanling Yu, Guoyou Liu, Jie Du, Lei Wang

Published in

Journal of molecular and cellular cardiology. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Icosapent ethyl, a high-purity ethyl ester of eicosapentaenoic acid (EPA), has demonstrated cardiovascular benefit in clinical trials; however, its effects on post-myocardial infarction (MI) cardiac remodeling and the underlying cellular mechanisms remain incompletely understood. Here, we investigated the role of icosapent ethyl in regulating post-MI remodeling using a murine MI model with myeloid-specific deletion of the omega-3 fatty acid receptor GPR120. Icosapent ethyl treatment significantly improved survival, preserved left ventricular systolic function, attenuated adverse ventricular remodeling and interstitial fibrosis, reduced cardiomyocyte apoptosis, and preserved myocardial microvascular density after MI. The protective effects of icosapent ethyl were markedly attenuated in myeloid GPR120-deficient mice. Mechanistically, icosapent ethyl activated GPR120 signaling in myeloid cells, suppressed CXCL10 expression, and reduced recruitment of proinflammatory CXCR3+ leukocytes into the infarcted myocardium. Pharmacological inhibition of CXCR3 rescued adverse cardiac remodeling in myeloid GPR120-deficient mice, supporting a functional link between myeloid GPR120 activation and CXCR3-dependent inflammatory responses. These findings identify the myeloid GPR120-CXCL10/CXCR3 signaling axis as a critical immunomodulatory pathway by which icosapent ethyl improves post-MI cardiac remodeling, highlighting therapeutic potential of icosapent ethyl to limit inflammation-driven cardiac dysfunction after ischemic injury.

PMID:
42628912
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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