Plasma Exosomes From Patients With Acute Myocardial Infarction Induce A Pro-inflammatory Immune Response

Background: Emerging evidences have indicated that exosomes play important roles in inflammation.However,the biological roles of plasma exosomes in acute myocardial infarction(AMI)patients have remained largely unexplored.We hypothesized that endogenous plasma exosomes can contribute to the proinflammatory immune response in AMI patients.Objective: This study sought to isolate and characterize exosomes from AMI patients and healthy controls(HCs),evaluate their pro-inflammatory effect and identify the molecular mechanisms that may be involved.Methods: Exosomes were isolated from the plasma of AMI patients and HCs and were analyzed by scanning electron microscopy,protein marker expression,and Exosome Quantitation Assay.Human umbilical vein endothelial cells(HUVECs)were stimulated with plasma exosomes isolated from AMI patients and HCs for 24 h.Cell activity and lactate dehydrogenase(LDH)levels were used to assess cell damage.Production of interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α were measured to evaluate pro-inflammatory effect.And then we explored whether the classic NF-κB pathway was activated.Results: In the present study,we demonstrated that(1)the levels of plasma exosomes were significantly higher in AMI patients than in HCs;(2)plasma exosomes were internalized by HUVECs,and then play their biological effect;(3)AMI exosomes not only reduced the cell activity and increased LDH release,but also could induce a pro-inflammatory phenotype in HUVECs named P-HUVECs,which was manifested as the elevation of IL-1β,IL-6 and TNF-α mRNA and protein levels;(4)P-HUVECs induced by AMI exosomes were at least partly dependent on the activation of NF-κB signaling pathway.Conclusions: This study is the first evidence that plasma exosomes from patients with AMI have a certain pro-inflammatory property,and are able to initiate a significant immune inflammatory response at least partly depending on the activation of NF-κB signaling.