Lymph Node Exosomes Delivery Attenuates Myocardial Ischemia-Reperfusion Injury via Regulating PTEN-PI3K/Akt Pathway Mediated Myocardiocyte Apoptosis.

BACKGROUND: Ischemia/reperfusion (I/R) injury following acute myocardial infarction (AMI) induces myocardial apoptosis. Exosomes from KLF2-overexpressing endothelial cells (KLF2-EXO) dampened the effects of I/R injury. The intra-lymph node drainage pathway provides an alternative method to study the therapeutic effects of exosomes. In this study, we explored the role of intra-lymph node injection of KLF2-EXO in myocardial I/R injury. METHOD AND RESULT: Exosomes were isolated from KLF2-overexpressing mouse coronary endothelial cell supernatant via gradient centrifugation. The mice were subjected to ischemia and reperfusion, and an appropriate dosage of KLF2-EXO was administrated via intra-inguinal lymph node injection. KLF2-EXO attenuated I/R injury and alleviated myocardiocyte apoptosis in heart tissue, and immunofluorescence staining indicated KLF2-EXO could be transferred into the heart. MiRNA-sequencing of KLF2-EXO implicated that miRNA-486-5p (miR-486-5p) was a potent candidate mediator that inhibited myocardiocyte apoptosis, and the miR-486-5p antagomir reversed the effect. Further bioinformatics analysis and confirmation experiments revealed that PTEN functions as a downstream target and that the PTEN- PI3K/Akt pathway participates in the regulation of cardiomyocyte apoptosis. CONCLUSION: Our data demonstrated that intra-lymph node injection of KLF2-EXO attenuated myocardial I/R injury in mice by delivering miR-486-5p to target PTEN- PI3K/Akt pathway, which restrained myocardiocyte apoptosis. KLF2-EXO may serve as an alternative therapy for myocardial I/R injury.