Mesenchymal stem cell-derived extracellular vesicles as probable triggers of radiation-induced heart disease

Abstract

Background Radiation-induced heart disease has been reported, but the underlying mechanisms remain unclear. Mesenchymal stem cells (MSCs), also residing in the heart, are highly susceptible to radiation. We examined the hypothesis that the altered secretion of extracellular vesicles (EVs) from MSCs is the trigger of radiation-induced heart disease. Methods By exposing human placental tissue-derived MSCs to 5 Gy γ-rays, we then isolated EVs from the culture medium 48 h later and evaluated the changes in quantity and quality of EVs from MSCs after radiation exposure. The biological effects of EVs from irradiated MSCs on HUVECs and H9c2 cells were also examined. Results Although the amount and size distribution of EVs did not differ between the nonirradiated and irradiated MSCs, miRNA sequences indicated many upregulated or downregulated miRNAs in irradiated MSCs EVs. In vitro experiments using HUVEC and H9c2 cells showed that irradiated MSC-EVs decreased cell proliferation (P < 0.01), but increased cell apoptosis and DNA damage. Moreover, irradiated MSC-EVs impaired the HUVEC tube formation and induced calcium overload in H9c2 cells. Conclusions EVs released from irradiated MSCs show altered miRNA profiles and harmful effects on heart cells, which provides new insight into the mechanism of radiation-related heart disease risks.

Advances in multimodality imaging and the application of new cardiac imaging technologies for radiation‐induced heart disease

“…This transmural penetration of the extracellular matrix is related to the pathological accumulation of immune cells (macrophages and mast cells) and changes in calcium flow in cardiomyocytes, leading to systolic and diastolic dysfunction and affecting the cardiac conduction system [19]. Ultimately, this leads to disease, such as myocarditis, ventricular enlargement, myocardial contraction weakness, arteriosclerosis, valve stenosis, and pericarditis [20,21].…”

Tissue Reactions and Mechanism in Cardiovascular Diseases Induced by Radiation

“…The types of cell death of HUVECs induced by radiation include apoptosis [ 38 ], pyroptosis [ 39 ], and ferroptosis [ 40 ]. In addition to the direct targeting effects of radiation on HUVECs, significant radiation-mimic effects can also be evoked by the extracellular vesicles or exosomes, secreted from other types of tissue cells with or without IR, such as mesenchymal stem cells [ 41 ] and cancer cells [ 42 , 43 , 44 ]. This form of effect is called the radiation bystander effect [ 43 , 45 ], and it may have important practical implications in clinical cancer radiotherapy.…”