AUTHOR=Cui Wen-Wen , Ye Cong , Wang Kai-Xuan , Yang Xu , Zhu Pei-Yan , Hu Kan , Lan Ting , Huang Lin-Yan , Wang Wan , Gu Bing , Yan Chen , Ma Ping , Qi Su-Hua , Luo Lan 

TITLE=Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.864188

DOI=10.3389/fcvm.2022.864188

ISSN=2297-055X

ABSTRACT=<p>Thoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while <italic>Momordica. charantia</italic> and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of <italic>Momordica. charantia</italic>-derived EVs-like nanovesicles (MCELNs) against RIHD. Using density gradient centrifugation, we successfully isolated MCELNs with similar shape, size, and markers as EVs. Confocal imaging revealed that rat cardiomyocytes H9C2 cells internalized PKH67 labeled MCELNs time-dependently. <italic>In vitro</italic> assay identified that MCELNs promoted cell proliferation, suppressed cell apoptosis, and alleviated the DNA damage in irradiated (16 Gy, X-ray) H9C2 cells. Moreover, elevated mitochondria ROS in irradiated H9C2 cells were scavenged by MCELNs, protecting mitochondria function with re-balanced mitochondria membrane potential. Furthermore, the phosphorylation of ROS-related proteins was recovered with increased ratios of p-AKT/AKT and p-ERK/ERK in MCELNs treated irradiated H9C2 cells. Last, intraperitoneal administration of MCELNs mitigated myocardial injury and fibrosis in a thoracic radiation mice model. Our data demonstrated the potential protective effects of MCELNs against RIHD. The MCELNs shed light on preventive regime development for radiation-related toxicity.</p>