Macrophage, a potential targeted therapeutic immune cell for cardiomyopathy

Abstract

Cardiomyopathy is a major cause of heart failure, leading to systolic and diastolic dysfunction and promoting adverse cardiac remodeling. Macrophages, as key immune cells of the heart, play a crucial role in inflammation and fibrosis. Moreover, exogenous and cardiac resident macrophages are functionally and phenotypically different during cardiac injury. Although experimental evidence has shown that macrophage-targeted therapy is promising in cardiomyopathy, clinical translation remains challenging. In this article, the molecular mechanism of macrophages in cardiomyopathy has been discussed in detail based on existing literature. The issues and considerations of clinical treatment strategies for myocardial fibrosis has also been analyzed.

Interplay between Senescence and Macrophages in Diabetic Cardiomyopathy: A Review of the Potential Role of GDF-15 and Klotho

“…DCM is associated with an imbalanced M1-to-M2-macrophage ratio [15]. Multiple studies have reported a predominantly M1 phenotype in DCM, contributing to cardiac fibrosis and impaired cardiac function [15,41].…”

“…DCM is associated with an imbalanced M1-to-M2-macrophage ratio [15]. Multiple studies have reported a predominantly M1 phenotype in DCM, contributing to cardiac fibrosis and impaired cardiac function [15,41]. M1 macrophage-activated pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, promote inflammation, oxidative stress, and cardiomyocyte apoptosis.…”

“…Dyslipidemia promotes the production of pro-inflammatory lipid mediators, such as oxidized low-density lipoprotein, leading to M1 polarization. AGEs, formed by non-enzymatic protein glycation, activate receptors that promote pro-inflammatory responses, thereby impairing M2 macrophage polarization and function [15]. Lipids have a substantial effect on macrophage polarization and influence macrophage functions.…”

“…Numerous etiological factors contributing to the development and progression of DCM have been identified, including hyperglycemia, hyperinsulinemia, insulin resistance, mitochondrial dysfunction, altered calcium homeostasis, increased production and accumulation of advanced glycation end products (AGEs) in cardiac cells as a consequence of prolonged hyperglycemia, and inflammation [13]. Senescence, a state of irreversible cell cycle arrest, and macrophage-mediated inflammation have emerged as key processes in the development and progression of diabetic cardiomyopathy [14,15]. Recent studies have implicated growth differentiation factor-15 (GDF-15) and Klotho, two factors involved in stress responses and aging, as potential regulators in this complex interplay of processes [16,17] (Figure 1).…”

Exploring the cardiac ECM during fibrosis: A new era with next-gen proteomics

“…M1 macrophages mediate the removal of dead cells and ECM debris. Cytokines secreted from M1 macrophages gradually increase the infarct size ( Duncan et al, 2020 ; Chen et al, 2022 ). Contrastingly, M2 macrophages are involved in drafting fibroblasts to the injury site and secreting pro-fibrotic mediators such as IL-10, TGF-β, and platelet-derived growth factor (PDGF) ( Frangogiannis, 2019 ; Viola et al, 2019 ; Kim et al, 2021 ).…”