A Novel Anticancer Therapeutic Strategy to Target Autophagy Accelerates Radiation-Associated Atherosclerosis

Yuan, Ruosen; Sun, Zhe; Cai, Jiali; Yang, Xiaoxiao; Zhang, Weifeng; Wu, Caizhe; Shen, Yejiao; Yin, Anwen; Wang, Xia; Cai, Xu-Wei; Fu, Xiaolong; Shen, Linghong; He, Ben

doi:10.1016/j.ijrobp.2020.09.007

Cited by 10 publications

(6 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite multiple studies investigating the health impacts of ionizing radiation, questions remain regarding the effects of exposure on cardiovascular diseases. Both epidemiological [1][2][3][4] and experimental studies [5][6][7][8][9][10][11] revealed that exposure to high doses of ionizing radiation has detrimental cardiovascular outcomes. However, when it comes to low dose ionizing radiation (LDIR), epidemiological studies have not provided a clear message.…”

Section: Introductionmentioning

confidence: 99%

Exposure to Low to Moderate Doses of Ionizing Radiation Induces A Reduction of Pro-Inflammatory Ly6chigh Monocytes and a U-Curved Response of T Cells in APOE -/- Mice

et al. 2021

View full text Add to dashboard Cite

Low dose ionizing radiation (LDIR) is known to have a protective effect on atherosclerosis in rodent studies, but how it impacts different cells types involved in lesion formation remains incompletely understood. We investigated the immunomodulatory response of different doses and dose-rates of irradiation in ApoE-/- mice. Mice were exposed to external γ rays at very low (1.4 mGy.h-1) or low (50 mGy.h-1) dose-rates, with cumulative doses spanning 50 to 1000 mGy. Flow cytometry of circulating cells revealed a significant decrease in pro-inflammatory Ly6CHi monocytes at all cumulative doses at low dose-rate, but more disparate effects at very low dose-rate with reductions in Ly6CHi cells at doses of 50, 100 and 750 mGy only. In contrast, Ly6CLo monocytes were not affected by LDIR. Similarly, proportions of CD4+ T cell subsets in the spleen did not differ between irradiated mice and non-irradiated controls, whether assessing CD25+FoxP3+ regulatory or CD69+ activated lymphocytes. In the aorta, gene expression of cytokines such as IL-1 and TGF-ß and adhesion molecules such as E-Selectin, ICAM-1, and VCAM-1 were reduced at the intermediate dose of 200 mGy. These results suggest that LDIR may reduce atherosclerotic plaque formation by selectively reducing blood pro-inflammatory monocytes and by impairing adhesion molecule expression and inflammatory processes in the vessel wall. In contrast, splenic T lymphocytes were not affected by LDIR. Furthermore, some responses to irradiation were nonlinear; reductions in aortic gene expression were significant at intermediate doses, but not at either highest or lowest doses. This work furthers our understanding of the impact of LDIR with different dose-rates on immune system response in the context of atherosclerosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Exposure to Low to Moderate Doses of Ionizing Radiation Induces A Reduction of Pro-Inflammatory Ly6chigh Monocytes and a U-Curved Response of T Cells in APOE -/- Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Several factors contribute to the development of atherosclerosis, and radiation is one of them. Patients who have had tumors treated with radiation have also been diagnosed with atherosclerosis [18,19]. HDL has been shown to protect against atherosclerosis; however, whether it can protect against radiation-induced atherosclerosis is not fully known.…”

Section: Discussionmentioning

confidence: 99%

HDL inhibited atherosclerosis induced by radiation injury

Xie¹,

Zhu²,

Wang³

et al. 2022

ScienceAsia

View full text Add to dashboard Cite

High-density lipoprotein (HDL) inhibits atherosclerosis development from radiation damage; nonetheless, the underlying mechanism is yet to be defined. This work studied patients treated with radiation along with cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients who received radiation after neck cancers participated, and their arterial function was monitored by a B ultrasound. Similarly, HDL and other blood lipid indexes were also investigated. Then, MAECs were isolated, cultured, and passed through MTT assay to test the HDL protective role on ultraviolet B (UVB) radiation along with western blotting to test some apoptosis protein expression and possible molecules. Patients with high HDL levels were significantly less likely to develop atherosclerosis. We observed that MAECs treated with UVB were damaged significantly. However, HDL reversed the cell damage in a dose-depended manner. Meanwhile, the apoptosis process was investigated, and it revealed that HDL prevented UVB-induced apoptosis. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) in addition to AKT phosphorylation in MAECs. These findings imply that HDL protects against UVB-induced apoptosis via activating the PI3K/AKT signaling pathway.

show abstract

“…These hazards to human body are quite serious, which can lead to death. There are many reasons for atherosclerosis; also radiation may be a potential factor because some head and neck tumor patients get radiation or some radiologic patient has got atherosclerosis [17,18]. HDL was considered as a very good protects to anti atherosclerosis, but whether the HDL also can protect radiation-induced atherosclerosis not fully consider.…”

Section: Discussionmentioning

confidence: 99%

HDL Inhibited Atherosclerosis Induced by Radiation Injury

Xie¹,

Zhu

Wang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background- HDL inhibits atherosclerosis development from radiation damage; however, the mechanism for this process has not been fully defined. Methods- This study used radiation patients and cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients from oncology department of Jingzhou hospital who have got radiation after neck cancers, the arterial function was monitored by B ultrasound, HDL and other blood lipid indexes were tested.Then, MAECs were isolated and cultured, MTT assay was used to test the HDL protective role on UVB radiation, along with this, western blotting was proceed to test some apotosis protein expression and possible molecular.Results- Firstly, those patients with high HDL levels were less likely to develop atherosclerosis, with statistical differences. We observed that MAECs treated with UVB was damaged significantly; HDL reversed the cell damage as dose-depended manner. At mean time, the apoptosis process was assessed and found that HDL inhibited the apoptosis caused by UVB. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation in MAECs.Conclusion- These results suggest that HDL protected UVB-mediated appotosis by activation of a mechanism involving PI3K/Akt signal pathway.

show abstract

A Novel Anticancer Therapeutic Strategy to Target Autophagy Accelerates Radiation-Associated Atherosclerosis

Cited by 10 publications

References 46 publications

Exposure to Low to Moderate Doses of Ionizing Radiation Induces A Reduction of Pro-Inflammatory Ly6chigh Monocytes and a U-Curved Response of T Cells in APOE -/- Mice

Exposure to Low to Moderate Doses of Ionizing Radiation Induces A Reduction of Pro-Inflammatory Ly6chigh Monocytes and a U-Curved Response of T Cells in APOE -/- Mice

HDL inhibited atherosclerosis induced by radiation injury

HDL Inhibited Atherosclerosis Induced by Radiation Injury

Contact Info

Product

Resources

About