Basic/Translational Science -> Cell Physiology, Pharmacology, and Signaling D-PO02 - Poster Session II (ID 47) Poster

D-PO02-024 - Long Noncoding Rna Uca1 From Hypoxia-conditioned Hmsc-derived Exosomes Acted As A Novel Exerkine For Cardioprotection Through Targeting Mir-873-5p/xiap Axis (ID 166)

 F. Zhang: Nothing relevant to disclose.


Background: Previous study indicated that exosomal long noncoding RNA urothelial carcinoma associated 1 (lncRNA-UCA1) increased significantly in anoxic environment.
Objective: To investigate the effects of lncRNA-UCA1 from hypoxia-conditioned hMSCs-derived exosomes (Hypo-Exo) on cardioprotection and its underlying mechanisms.
Methods: Circulating exosomes were isolated from the plasma of acute myocardial infarction (AMI) patients and volunteers. Human mesenchymal stem cells (hMSCs) were subjected to a hypoxia or normoxia culture, and exosomes were subsequently collected. Cell viability and apoptosis were assessed using a cell count kit and flow cytometry/TUNEL. Hypo-Exo or normoxia-conditioned hMSCs-derived Exo (Nor-Exo) were administered to AMI rats. After 28 days, Masson’s trichrome staining and echocardiography were used to evaluate the fibrotic area and heart function. LncRNA-knockdown-Hypo-Exo was injected in a rat AMI model, and the cardiac function, cardiomyocyte apoptosis, and fibrotic area were analyzed. Mechanistically, the interaction of lncRNA with miRNA was examined using luciferase reporter assays.
Results: LncRNA-UCA1 was higher in AMI patients than in healthy persons. LncRNA-UCA1 was significantly enriched in Hypo-Exo compared with Nor-Exo. When Nor-Exo was cocultured with the Hypoxic H9c2 cell, cell viability was significantly increased, while cell apoptosis was attenuated compared with the Nor-Exo group. Hypo-Exo significantly reduced the fibrotic area and increased the left ventricular ejection fraction (LVEF) after AMI compared with Nor-Exo. After silencing lncRNA-UCA1, it significantly blunted the protective effects in hypoxia cardiomyocytes and AMI rats. Because of competitive binding of lncRNA-UCA1 to miR-873-5p, the suppressive activity of the antiapoptotic gene X-linked inhibitor of apoptosis protein (XIAP) by miR-873-5p was reduced.
Conclusion: This study demonstrated that lncRNA-UCA1 from hMSCs-derived Exo played a cardioprotective role through the miR873-5p/XIAP axis and that exosomal lncRNA-UCA1 may be a potential biomarker for AMI diagnosis.