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

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

doi:10.3389/fcvm.2022.864188

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

Front Cardiovasc Med. 2022 Apr 18:9:864188. doi: 10.3389/fcvm.2022.864188. eCollection 2022.

Authors

Wen-Wen Cui¹, Cong Ye¹, Kai-Xuan Wang¹, Xu Yang^{1

2}, Pei-Yan Zhu¹, Kan Hu², Ting Lan¹, Lin-Yan Huang¹, Wan Wang¹, Bing Gu³, Chen Yan⁴, Ping Ma², Su-Hua Qi¹, Lan Luo¹

Affiliations

¹ Medical Technology School, Xuzhou Medical University, Xuzhou, China.
² Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
³ Department of Laboratory Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
⁴ Department of Rheumatology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

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 Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of Momordica. charantia-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. In vitro 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.

Keywords: DNA damage; H9C2 cells; Momordica. charantia-derived extracellular vesicles-like nanovesicles; mitochondria dysfunction; radiation-induced heart disease.