Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis

Abstract Cardiac shock wave therapy (CSWT) as an effectual therapy can activate the function of exosomes to a certain extent. Here, we attempted to examine the role of CSWT in exosome released from ischemic cardiomyocytes and its function in myocardial ischemia recovery. The exosomes derived from OG...

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Main Authors: Lizhou Wu, Zhan Li, Wenhui Song, Li Zhang, Kuan Li, Haiyan Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00104-4
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author Lizhou Wu
Zhan Li
Wenhui Song
Li Zhang
Kuan Li
Haiyan Wang
author_facet Lizhou Wu
Zhan Li
Wenhui Song
Li Zhang
Kuan Li
Haiyan Wang
author_sort Lizhou Wu
collection DOAJ
description Abstract Cardiac shock wave therapy (CSWT) as an effectual therapy can activate the function of exosomes to a certain extent. Here, we attempted to examine the role of CSWT in exosome released from ischemic cardiomyocytes and its function in myocardial ischemia recovery. The exosomes derived from OGD/R-treated H9c2 (H9c2-OGD/R-Exo) and CSWT-treated OGD/R-stimulated H9c2 (CSWT-H9c2-OGD/R-Exo) were performed with small RNA sequencing to determine miRNAs that differentially expressed. After miR-98-5p inhibitor transfection, H9c2 were subjected to OGD/R and co-cultured with CSWT-H9c2-OGD/R-Exo, the cell viability, LDH and cell apoptosis were assessed. The transfected HUVECs were co-cultured with CSWT-H9c2-OGD/R-Exo, then HUVECs viability, angiogenesis, migration and invasion were assessed. The luciferase reporter gene assay was conducted to prove the targeting relation between miR-98-5p and FOXN3. miR-98-5p was highly enriched in CSWT-H9c2-OGD/R-Exo in compared with H9c2-OGD/R-Exo. CSWT-H9c2-OGD/R-Exo could improve cell viability, inhibit LDH and cell apoptosis. And miR-98-5p released by CSWT-H9c2-OGD/R-Exo promoted HUVECs viability, angiogenesis, migration and invasion. Further FOXN3 was defined as the downstream target gene of miR-98-5p, and miR-98-5p overexpression decreased FOXN3 expression in HUVECs. Besides, the suppression effects of miR-98-5p inhibitor on HUVECs proliferation, angiogenesis and metastasis was partly blunted by FOXN3 silencing. miR-98-5p released from CSWT-H9c2-OGD/R-Exo promoted HUVECs proliferation, angiogenesis and metastasis through directly targeting and suppressing FOXN3 expression.
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spelling doaj-art-50f8a0b53f37418d90a2d91ffa7e95092025-08-20T02:55:31ZengNature PortfolioScientific Reports2045-23222025-04-0115111110.1038/s41598-025-00104-4Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesisLizhou Wu0Zhan Li1Wenhui Song2Li Zhang3Kuan Li4Haiyan Wang5Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalDepartment of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalDepartment of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalThe Department of Immunology, School of Basic Medicine, Qingdao UniversityClinical Medical Institute, Xinjiang Medical UniversityDepartment of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan HospitalAbstract Cardiac shock wave therapy (CSWT) as an effectual therapy can activate the function of exosomes to a certain extent. Here, we attempted to examine the role of CSWT in exosome released from ischemic cardiomyocytes and its function in myocardial ischemia recovery. The exosomes derived from OGD/R-treated H9c2 (H9c2-OGD/R-Exo) and CSWT-treated OGD/R-stimulated H9c2 (CSWT-H9c2-OGD/R-Exo) were performed with small RNA sequencing to determine miRNAs that differentially expressed. After miR-98-5p inhibitor transfection, H9c2 were subjected to OGD/R and co-cultured with CSWT-H9c2-OGD/R-Exo, the cell viability, LDH and cell apoptosis were assessed. The transfected HUVECs were co-cultured with CSWT-H9c2-OGD/R-Exo, then HUVECs viability, angiogenesis, migration and invasion were assessed. The luciferase reporter gene assay was conducted to prove the targeting relation between miR-98-5p and FOXN3. miR-98-5p was highly enriched in CSWT-H9c2-OGD/R-Exo in compared with H9c2-OGD/R-Exo. CSWT-H9c2-OGD/R-Exo could improve cell viability, inhibit LDH and cell apoptosis. And miR-98-5p released by CSWT-H9c2-OGD/R-Exo promoted HUVECs viability, angiogenesis, migration and invasion. Further FOXN3 was defined as the downstream target gene of miR-98-5p, and miR-98-5p overexpression decreased FOXN3 expression in HUVECs. Besides, the suppression effects of miR-98-5p inhibitor on HUVECs proliferation, angiogenesis and metastasis was partly blunted by FOXN3 silencing. miR-98-5p released from CSWT-H9c2-OGD/R-Exo promoted HUVECs proliferation, angiogenesis and metastasis through directly targeting and suppressing FOXN3 expression.https://doi.org/10.1038/s41598-025-00104-4CSWTExosomesAngiogenesisMyocardial infarction
spellingShingle Lizhou Wu
Zhan Li
Wenhui Song
Li Zhang
Kuan Li
Haiyan Wang
Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis
Scientific Reports
CSWT
Exosomes
Angiogenesis
Myocardial infarction
title Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis
title_full Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis
title_fullStr Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis
title_full_unstemmed Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis
title_short Cardiac shock wave therapy-induced exosome derived from OGD/R-treated H9c2 cells carrying miR-98-5p promote HUVECs angiogenesis
title_sort cardiac shock wave therapy induced exosome derived from ogd r treated h9c2 cells carrying mir 98 5p promote huvecs angiogenesis
topic CSWT
Exosomes
Angiogenesis
Myocardial infarction
url https://doi.org/10.1038/s41598-025-00104-4
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AT kuanli cardiacshockwavetherapyinducedexosomederivedfromogdrtreatedh9c2cellscarryingmir985ppromotehuvecsangiogenesis
AT haiyanwang cardiacshockwavetherapyinducedexosomederivedfromogdrtreatedh9c2cellscarryingmir985ppromotehuvecsangiogenesis