Interleukin-1β polarization in M1 macrophage mediates myocardial fibrosis in diabetes.

Wenli Guo, Chen Yang, Jiawei Zou, Tingting Yu, Mingde Li, Ruilin He, Keyang Chen, Rafaela C R Hell, Eric R Gross, Xin Zou, Yao Lu

International immunopharmacology 2024 Apr 20

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Diabetes is a global health problem whose common complication is diabetic cardiomyopathy, characterized by chronic inflammation of the heart muscle. Macrophages are the main white blood cells found in the resting heart. Therefore, we investigated the underling mechanism of macrophage on myocardial fibrosis in diabetes. Here, echocardiography was utilized to evaluate cardiac function, and the degree of myocardial fibrosis was assessed using Masson's trichrome staining, followed by single-cell RNA sequencing (scRNA-seq) to analyze the phenotype, function, developmental trajectory, and interactions between immune cells, endothelial cells (ECs), and fibroblasts (FBs) in the hearts of db/db mice at different stages of diabetes. Macrophages and cardiac fibroblasts were also co-cultured in order to study the signaling between macrophages and fibroblasts. We found that with the development of diabetes mellitus, myocardial hypertrophy and fibrosis occurred that was accompanied by cardiac dysfunction. A significant proportion of immune cells, endothelial cells, and fibroblasts were identified by RNA sequencing. The most significant changes observed were in macrophages, which undergo M1 polarization and are critical for oxidative stress and extracellular matrix (ECM) formation. We further found that M1 macrophages secreted interleukin-1β (IL-1β), which interacted with the receptor on the surface of fibroblasts, to cause myocardial fibrosis. In addition, crosstalk between M1 macrophages and endothelial cells also plays a key role in fibrosis and immune response regulation through IL-1β and corresponding receptors. M1 macrophages mediate diabetic myocardial fibrosis through interleukin-1β interaction with fibroblasts. Copyright © 2024 Elsevier B.V. All rights reserved.

Citation

Wenli Guo, Chen Yang, Jiawei Zou, Tingting Yu, Mingde Li, Ruilin He, Keyang Chen, Rafaela C R Hell, Eric R Gross, Xin Zou, Yao Lu. Interleukin-1β polarization in M1 macrophage mediates myocardial fibrosis in diabetes. International immunopharmacology. 2024 Apr 20;131:111858