M2b macrophages protect against doxorubicin induced cardiotoxicity via alternating autophagy in cardiomyocytes

Abstract

Objective Doxorubicin (DOX) is an anthracycline antibiotic which is widely used for the treatment of various cancers, while the dose-related cardiotoxicity limits its potential therapeutic application. The underlying mechanism of DOX induced cardiotoxicity is complex and remains elusive. Our previous studies have shown that M2b macrophage plays an important role in reducing inflammation due to ischemic reperfusion injury in the myocardium. The purpose of this study was to investigate the potential protective role of M2b macrophages in DOX induced cardiotoxicity. Methods In vivo, we conducted DOX induced cardiac injury in C57BL/6 mice and treated them with M2b macrophages. Then, the mice were examined by echocardiography. The heart specimens were harvested for histological examination, transmission electron microscope analysis, and autophagy molecules evaluation. In vitro, HL-1 cardiac cell lines treated with DOX were cocultured with or without M2b macrophages. Then, Autophagy related genes and protein expression were assessed by real-time quantitative PCR and western blot; cell proliferation was assessed by cell counting kit-8. Results We found that M2b macrophages can improve cardiac function and alleviate cardiac injury in DOX induced cardiac injury mice. M2b macrophages can enhance cardiac autophagy levels both in vivo and in vitro in DOX induced cardiac injury model. In addition, this protective effect can be blocked by an autophagy inhibitor. Conclusion Our study shows that M2b macrophages can help attenuate the DOX induced cardiotoxicity by regulating the autophagy level of cardiomyocytes.

Chemotherapy activates inflammasomes to cause inflammation-associated bone loss

“…The effects of doxorubicin on macrophages have been reported ( Chen et al, 2023 ; Saleh et al, 2021 ). To test the hypothesis that these cells were implicated in the inflammatory phenotype of mice treated with doxorubicin, we treated bone marrow-derived macrophages (BMMs) with lipopolysaccharide (LPS) for 3 hr to induce the expression of inflammasome components ( Wang et al, 2021 ), then with various concentrations of this drug for 16 hr.…”

Chemotherapy activates inflammasomes to cause inflammation-associated bone loss

“…The effects of doxorubicin on macrophages have been reported (Chen et al, 2023, Saleh et al, 2021). To test the hypothesis that these cells were implicated in the inflammatory phenotype of mice treated with doxorubicin, we treated bone marrow-derived macrophages (BMMs) with lipopolysaccharide (LPS) for 3 hours to induce the expression of inflammasome components (Wang et al, 2021), then with various concentrations of this drug for 16 hours.…”

Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets

“…31 Additionally, with a constant number of macrophages, it is generally believed that the polarization of macrophages towards the M2 phenotype can suppress inflammation over time, leading to a reduction in fibrosis. 32,33 Macrophages can also regulate fibrosis through phagocytosis and modulation of inflammatory responses. While suppressing fibrosis by removing necrotic tissue and temporary matrix through phagocytosis, 31 some proinflammatory or anti-inflammatory factors secreted by macrophages can directly act on interleukin 1 receptor (IL-1R), IL-6R complex, and angiotensin-II type 1 receptor (AT1R) on fibroblasts, or induce the increase of pro-fibrotic factors, thereby promoting fibrosis.…”

“…This transfer of mitochondria may explain why the adoptive transfer of M2 macrophages can alleviate myocardial fibrosis. 32,33 Diabetic cardiomyopathy. Diabetic cardiomyopathy is defined as myocardial structural and functional abnormalities in diabetics, with metabolic disorders and myocardial fibrosis being prominent features.…”