Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation after acute myocardial infarction through JAK1-STAT1 signaling

Zhang, Jishou; Xu, Yao; Wei, Cheng; Yin, Zheng; Pan, Wei; Zhao, Mengmeng; Ding, Wen; Xu, Shuwan; Liu, Jianfang; Yu, Junping; Ye, Jing; Ye, Di; Qin, Juan-Juan; Wan, Jun; Wang, Menglong

doi:10.1007/s00018-023-04974-7

Cited by 2 publications

(1 citation statement)

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“…Myocardial infarction (MI) resulting from coronary artery disease remains a prominent global health concern and is associated with high morbidity and mortality rates. , MI triggers an inflammatory response, which is crucial in the cardiac repair process. − The inflammation reaction is initiated with the rapid recruitment of neutrophils (the front-line cells of the innate immune system), followed by the involvement of circulating monocytes. , This coordinated infiltration is essential for digesting and clearing damaged cells and extracellular matrix (ECM), facilitating the transition to reparative and proliferative states . Ultimately, the scar formation and adaptive remodeling responses help preserve cardiac function. , However, dysregulated inflammation for a prolonged duration can lead to sustained tissue damage, cardiac fibrosis, and adverse remodeling. − Therefore, modulating the inflammatory reaction for effective heart repair may be critical for successful MI treatment.…”

Section: Introductionmentioning

confidence: 99%

Annexin A1-Loaded Alginate Hydrogel Promotes Cardiac Repair via Modulation of Macrophage Phenotypes after Myocardial Infarction

Zhang,

Shao,

et al. 2024

ACS Biomater. Sci. Eng.

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Myocardial infarction (MI) is associated with inflammatory reaction, which is a pivotal component in MI pathogenesis. Moreover, excessive inflammation post-MI can lead to cardiac dysfunction and adverse remodeling, emphasizing the critical need for an effective inflammation-regulating treatment for cardiac repair. Macrophage polarization is crucial in the inflammation process, indicating its potential as an adjunct therapy for MI. In this study, we developed an injectable alginate hydrogel loaded with annexin A1 (AnxA1, an endogenous anti-inflammatory and pro-resolving mediator) for MI treatment. In vitro results showed that the composite hydrogel had good biocompatibility and consistently released AnxA1 for several days. Additionally, this hydrogel led to a reduced number of pro-inflammatory macrophages and an increased proportion of pro-healing macrophages via the adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of the rapamycin (mTOR) axis. Furthermore, the intramyocardial injection of this composite hydrogel into a mouse MI model effectively modulated macrophage transition to pro-healing phenotypes. This transition mitigated early inflammatory responses and cardiac fibrosis, promoted angiogenesis, and improved cardiac function. Therefore, our study findings suggest that combining biomaterials and endogenous proteins for MI treatment is a promising approach for limiting adverse cardiac remodeling, preventing cardiac damage, and preserving the function of infarcted hearts.

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