Peripheral Serum Exosomes Isolated from Patients with Acute Myocardial Infarction Promote Endothelial Cell
Shasha Duan1,2,3, Chao Wang1,2, Xiangli Xu4
1Department of Ultrasound, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
Insights
Exosomes from acute myocardial infarction (AMI) patients promote blood vessel growth by delivering miR-126-3p. This microRNA targets TSC1, activating pathways that enhance angiogenesis, crucial for heart function recovery.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Exosome Biology
Background:
- Angiogenesis is vital for myocardial function and recovery after acute myocardial infarction (AMI).
- The role of peripheral exosomes in mediating angiogenic signaling post-AMI is not fully understood.
- Exosomes are recognized for their significant involvement in regulating angiogenesis.
Purpose of the Study:
- To investigate the impact of exosomes from AMI patients on angiogenesis.
- To identify the specific downstream molecular pathways involved in exosome-mediated angiogenic signal transduction.
Main Methods:
- Serum exosomes were isolated from AMI patients (AMI-Exo) and healthy controls (Con-Exo).
- Exosomes were tested in vitro (HUVECs, aortic rings) and in vivo (mouse models of hind-limb ischemia and AMI).
- Quantitative RT-PCR, knockdown, and overexpression studies were used to analyze miR-126-3p and its targets.
Main Results:
- AMI-Exo significantly enhanced endothelial cell proliferation, migration, and tube formation compared to Con-Exo.
- Increased levels of miR-126-3p were found in AMI-Exo, and its modulation affected angiogenic responses.
- miR-126-3p directly targets TSC1, leading to mTORC1 activation and increased HIF-1α and VEGFA, promoting angiogenesis.
Conclusions:
- Peripheral exosomes from AMI patients promote angiogenesis.
- The miR-126-3p/TSC1/mTORC1/HIF-1α pathway is a key mechanism by which AMI exosomes enhance angiogenesis.
- These findings offer novel insights into exosome function in post-AMI recovery.
Purpose:
Angiogenesis is required for improving myocardial function and is a key factor in long-term prognosis after an acute myocardial infarction (AMI). Although exosomes are known to play a crucial role in angiogenesis, the role of peripheral exosomes in angiogenic signal transduction in patients with AMI remains unclear. Here, we explored the effect of exosomes extracted from the peripheral serum of AMI patients on angiogenesis and elucidated the downstream pathways.
Patients And Methods:
Serum exosomes were obtained from patients with AMI (AMI-Exo) and healthy individuals (Con-Exo). The exosomes were cocultured with human umbilical vein endothelial cells (HUVECs) in vitro, with aortic rings ex vivo, and were used to treat mouse hind-limb ischemia and mouse AMI model in vivo.
Results:
AMI-Exo raised HUVEC proliferation, tube formation, and migration, and enhanced microvessel sprouting from aortic rings compared to Con-Exo, both in vitro and ex vivo. Quantitative reverse transcription-polymerase chain reaction revealed that the abundance of miR-126-3p, a crucial regulator of angiogenesis, was increased in AMI-Exo. The inhibition of miR-126-3p decreased the benefits of AMI-Exo treatment, and miR-126-3p upregulation enhanced the benefits of Con-Exo treatment in HUVECs, aortic rings, the mouse hind-limb ischemia model, and the mouse AMI model. Knockdown and overexpression analyses revealed that miR-126-3p regulated angiogenesis in HUVECs by directly targeting tuberous sclerosis complex 1 (TSC1). Moreover, we found that miR-126-3p could inhibit TSC1 expression, which further activated mTORC1 signaling and increased HIF-1α and VEGFA expression, ultimately promoting angiogenesis.
Conclusion:
Collectively, our results provide a novel understanding of the function of exosomes in angiogenesis post AMI. We demonstrated that exosomes from the peripheral serum of AMI patients promote angiogenesis via the miR-126-3p/TSC1/mTORC1/HIF-1α signaling pathway.
