Exosomes as a messager to regulate the crosstalk between macrophages and cardiomyocytes under hypoxia conditions
Zenglei Zhang1,2,3, Yanyan Xu1,2,3, Chang Cao1,2,3
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Insights
Cardiomyocyte exosomes mediate communication between heart cells and macrophages. Hypoxia-altered exosomes from heart cells can polarize macrophages, with M2 macrophages reducing heart cell death, highlighting exosomes
Area of Science:
- Cardiovascular Biology
- Cellular Communication
- Exosome Biology
Background:
- Cardiomyocyte-derived exosomes play roles in coronary artery disease by modulating macrophage phenotypes.
- The precise mechanisms of cardiomyocyte-macrophage crosstalk remain incompletely understood.
- Exosomes are critical mediators of intercellular communication in cardiovascular contexts.
Purpose of the Study:
- To investigate cardiomyocyte-macrophage interactions via exosome communication under hypoxic conditions.
- To evaluate the capacity of exosomes from hypoxic cardiomyocytes (Hypo-Exo) to polarize macrophages.
- To determine the impact of alternatively activated macrophages (M2) on hypoxic cardiomyocytes.
Main Methods:
- Isolation and characterization of exosomes from cardiomyocytes under normal (Nor-Exo) and hypoxic (Hypo-Exo) conditions.
- Co-culture experiments with exosomes and RAW264.7 macrophage cell lines.
- Analysis of macrophage polarization (M1/M2) induced by exosomes.
- Assessment of M2 macrophage effects on hypoxic cardiomyocyte apoptosis.
- Isolation and analysis of exosomes from human controls (hNor-Exo) and acute myocardial infarction patients (hAMI-Exo).
Main Results:
- Hypoxia enhanced transforming growth factor-beta (TGF-β) production in H9c2 cell-derived exosomes.
- Nor-Exo and Hypo-Exo induced M1 and M2 macrophage polarization, respectively.
- Circulating exosomes from acute myocardial infarction patients (hAMI-Exo) altered macrophage polarization compared to normal controls (hNor-Exo).
- Polarized M2 macrophages demonstrated a protective effect by reducing cardiomyocyte apoptosis.
Conclusions:
- Exosomes derived from cardiomyocytes under hypoxia exhibit altered profiles, influencing macrophage polarization.
- Exosomes act as key modulators in the inflammatory response following cardiac injury.
- Exosome-mediated communication between cardiomyocytes and macrophages is a crucial mechanism in cardiac oxidative stress injury and repair.
Abstract:
Recent studies have confirmed that cardiomyocyte-derived exosomes have many pivotal biological functions, like influencing the progress of coronary artery disease via modulating macrophage phenotypes. However, the mechanisms underlying the crosstalk between cardiomyocytes and macrophages have not been fully characterized. Hence, this study aimed to observe the interaction between cardiomyocytes under hypoxia and macrophages through exosome communication and further evaluate the ability of exosomes derived from cardiomyocytes cultured under hypoxic conditions (Hypo-Exo) to polarize macrophages, and the effect of alternatively activated macrophages (M2) on hypoxic cardiomyocytes. Our results revealed that hypoxia facilitated the production of transforming growth factor-beta (TGF-β) in H9c2 cell-derived exosomes. Moreover, exosomes derived from cardiomyocytes cultured under normal conditions (Nor-Exo) and Hypo-Exo could induce RAW264.7 cells into classically activated macrophages (M1) and M2 macrophages respectively. Likewise, macrophage activation was induced by circulating exosomes isolated from normal human controls (hNor-Exo) or patients with acute myocardial infarction (hAMI-Exo). Thus, our findings support that the profiles of hAMI-Exo have been changed, which could regulate the polarization of macrophages and subsequently the polarized M2 macrophages reduced the apoptosis of cardiomyocytes in return. Based on our findings, we speculate that exosomes have emerged as important inflammatory response modulators regulating cardiac oxidative stress injury.
