{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:47:36Z","timestamp":1793908056206,"version":"4.8.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"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. Cardiovasc. Med."],"abstract":"<jats:p>Myocardial infarction (MI) triggers a systemic immune response involving bidirectional crosstalk between the injured heart and remote immune organs. However, the dynamic, multi-organ nature of this \u201cheart-immune axis\u201d remains poorly defined. By targeting specific aspects of the immune response, particularly the modulation of macrophage polarization and the attenuation of excessive inflammation, this strategy holds therapeutic potential for preserving cardiac function and enhancing long-term patient outcomes, thereby opening a new frontier in cardiovascular therapeutics. In this review, we propose a novel framework that divides post-MI immune response into three interconnected phases: inflammation, resolution, and remodeling. Within each phase, we delineate the bidirectional crosstalk mechanisms between the injured heart and immune organs via cytokine networks and hematopoietic progenitor mobilization. We then critically evaluate emerging immunomodulatory strategies, ranging from targeting CCR2\/CCL2 axis, promoting regulatory T cells, with emphasis on their mechanistic rationale, clinical trial progress, and major translational gaps. Unlike conventional anti-inflammatory approaches that suppress broad immune activity, axis-targeted immunomodulation aims to preserve or restore protective cardiac repair. This review provides a phase-specific, multi-organ, and therapeutically actionable roadmap of the heart-immune axis, offering new perspectives for next-generation MI therapies.<\/jats:p>","DOI":"10.3389\/fcvm.2026.1827666","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:57:38Z","timestamp":1779944258000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the heart-immune axis after myocardial infarction: from inflammation to immunomodulation"],"prefix":"10.3389","volume":"13","author":[{"given":"Li","family":"Huang","sequence":"first","affiliation":[{"name":"Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology","place":["Macau, Macau SAR, China"]},{"name":"The Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riping","family":"Xu","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology","place":["Macau, Macau SAR, China"]},{"name":"The Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Fan","sequence":"additional","affiliation":[{"name":"The Department of Coronary Heart Disease, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, 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