To evaluate the protective effect of miR-486-5p modified umbilical cord mesenchymal stem cells (UCMSC^miR-486) against radiation-induced heart damage (RIHD) and explore the mechanism.

20 Gy of ⁶⁰Coγ-ray was used to establish a model for radiation-induced cardiomyocytes and cardiac damage to mice before UCMSC^miR-486 (1×10⁶ cells per mouse) was treated after radiation. Cell proliferation was detected using CCK-8 kit 48 hours post-treatment. Apoptosis, changes of mitochondrial membrane potential, and the opening of the mitochondrial permeability transition pore of cardiomyocytes were detected by flow cytometry. Small animal ultrasound was used to detect and analyze the cardiac function of mice 42 days later. Changes of cardiac histopathology were detected via HE staining and Masson staining. The ultrastructure of myocardia was observed under a transmission electron microscope (TEM). Real-time quantitative PCR (RT-qPCR) and Western blotting were performed to detect the expressions of ferroptosis-related genes and proteins.

UCMSC^miR-486 markedly reduced radiation-induced apoptosis and especially reactive oxygen species (ROS) levels in AC16 cardiomyocytes and restored both mitochondrial membrane potential and membrane permeability. Intravenous administration of UCMSC^miR-486 via the tail vein significantly increased ejection fraction and shortening fraction in irradiated mouse hearts, decreased the area of myocardial fibrosis, and mitigated mitochondrial ultrastructural damage UCMSC^miR-486 could inhibit ferroptosis of radiated cardiomyocytes and cardiac tissues of mice by modulating the expressions of ferroptosis-related markers, especially acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4).

UCMSC^miR-486 can mitigate RIHD by inhibiting ferroptosis. This finding is expected to offer a new strategy for the clinical translation of mesenchymal stem cells.

Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co‐exist in the same individual. The present study aimed to investigate the role of high‐fat‐diet (HFD)‐induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E‐knockout (ApoE^−/−) mice.

Male ApoE^−/− mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1) and vascular endothelial growth factor levels were measured by enzyme‐linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence‐activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured.

At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (p = 0.0004), heavier tumors (p = 0.0235), more metastatic cancer in the lungs (p < 0.0001), a larger area of lung involved in metastatic cancer (p = 0.0031), and larger areas of atherosclerosis in the aorta (p < 0.0001). At Week 12, serum LOX‐1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (p = 0.0002, p = 0.0029, p = 0.0480, and p = 0.0106, respectively); this trend persisted until Week 15 (p = 0.0014, p = 0.0012, p = 0.0001, and p = 0.0204).

In this study, HFD‐induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD‐induced upregulation of LOX‐1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.