M2 macrophage-derived exosomes promote angiogenesis and improve cardiac function after myocardial infarction
Hongzhou Guo1,2, Zeya Li1, Bin Xiao1
1Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, 95 Yong'an Road, Beijing, 100050, P. R. China.
Background:
Myocardial infarction (MI) is a major cause of mortality and morbidity worldwide. The intercellular communication in post-infarction angiogenesis remains unclear.
Methods:
In this study, we explored the role and mechanism of action of M2 macrophage-derived exosomes (M2-exos) in angiogenesis after MI. M2-exos were harvested and injected intramyocardially at the onset of MI. Two distinct endothelial cells (ECs) were cultured with M2-exos to explore the direct effects on angiogenesis.
Results:
We showed that M2-exos improved cardiac function, reduced infarct size, and enhanced angiogenesis after MI. Moreover, M2-exos promoted angiogenesis in vitro; the molecules loaded in the vesicles were responsible for its proangiogenic effects. We further validated that higher abundance of miR-132-3p in M2-exos, which recapitulate their functions, was required for the cardioprotective effects exerted by M2-exos. Mechanistically, miR-132-3p carried by M2-exos down-regulate the expression of THBS1 through direct binding to its 3´UTR and the proangiogenic effects of miR-132-3p were largely reversed by THBS1 overexpression.
Conclusion:
Our findings demonstrate that M2-exos promote angiogenesis after MI by transporting miR-132-3p to ECs, and by binding to THBS1 mRNA directly and negatively regulating its expression. These findings highlight the role of M2-exos in cardiac repair and provide novel mechanistic understanding of intercellular communication in post-infarction angiogenesis.
Insights
M2 macrophage-derived exosomes (M2-exos) enhance cardiac repair after myocardial infarction (MI) by delivering miR-132-3p to endothelial cells, promoting angiogenesis and improving heart function.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Regenerative Medicine
Background:
- Myocardial infarction (MI) is a leading global cause of death.
- Intercellular communication's role in post-MI angiogenesis is not fully understood.
Purpose of the Study:
- To investigate M2 macrophage-derived exosomes (M2-exos) and their mechanism in promoting angiogenesis after MI.
- To elucidate the specific molecular pathways involved in M2-exo-mediated cardiac repair.
Main Methods:
- M2-exos were isolated and administered intramyocardially in a mouse model of MI.
- Endothelial cells (ECs) were treated with M2-exos in vitro to assess direct angiogenic effects.
- The role of miR-132-3p and its target THBS1 in M2-exo function was analyzed.
Main Results:
- M2-exos significantly improved cardiac function and reduced infarct size post-MI.
- M2-exos demonstrated pro-angiogenic effects both in vivo and in vitro.
- miR-132-3p within M2-exos was identified as crucial for cardioprotection, acting by downregulating THBS1 expression.
Conclusions:
- M2-exos promote angiogenesis after MI via miR-132-3p transfer to ECs.
- The M2-exo/miR-132-3p/THBS1 pathway is a key mechanism in cardiac repair.
- These findings offer insights into exosome-based therapies for cardiovascular diseases.
