Journal article
LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition
ISCIENCE, v 23(12), 101771
18 Dec 2020
PMID: 33376971
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Space radiation inhibits angiogenesis by twomechanisms depending on the linear energy transfer (LET). Using human 3D micro-vessel models, blockage of the early motile stage of angiogenesis was determined to occur after exposure to low LET ions (<3 KeV/AMU), whereas inhibition of the later stages occurs after exposure to high LET ions (>8 KeV/AMU). Strikingly, the combined effect is synergistic, detectible as low as 0.06 Gy making mixed ion space radiation more potent. Candidates for bystander transmission are microRNAs (miRNAs), and analysis on miRNA-seq data from irradiated mice shows that angiogenesis would in theory be downregulated. Further analysis of three previously identified miRNAs showed downregulation of their targets associated with angiogenesis and confirmed their involvement in angiogenesis pathways and increased health risks associated with cardiovascular disease. Finally, synthetic molecules (antagomirs) designed to inhibit the predicted miRNAs were successfully used to reverse the inhibition of angiogenesis.
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Details
- Title
- LET-Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of miRNAs that Drive Inhibition
- Publication Details
- ISCIENCE, v 23(12), 101771
- Publisher
- CELL PRESS; CAMBRIDGE
- Grant note
- We would like to thank Drs. Peter Guida, Adam Rusek, Michael Sivertz, and the NSRL team at BNL for their assistance and expertise with irradiation studies. This work was supported by NASA grants; NNX11AR03G, and NNX14AR22G awarded to P.G and the Translational Research Institute for Space Health through NASA Cooperative Agreement NNX16AO69A (T-0404) awarded to A.B.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000600670000017
- Scopus ID
- 2-s2.0-85097459087
- Other Identifier
- 991021860766604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biology