LET Dependent Low Dose and Synergistic Inhibition of Human Angiogenesis by Charged Particles: Validation of Mi RNAs that Drive Inhibition

• DOI: 10.2139/ssrn.3671930
• Publication Date: 2020-09-12T11:31:22Z
• Authors: Yen-Ruh Wuu; Burong Hu; Hazeem Okunola; Amber M. Paul; Elizabeth A. Blaber; Margareth Cheng-C...; Afshin Beheshti; Peter Grabham
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Science; Q; Radiation Biology; Molecular Biology; Space Sciences; Article; 3. Good health

Space Radiation inhibits angiogenesis by two mechanisms depending on the linear energy transfer (LET). Using human 3D micro-vessel models, blockage of early motile stage was determined to occur after exposure low LET ions (< 3 KeV/AMU) whereas inhibition later stages occurs high (> 8 KeV/AMU). Strikingly, combined effect is synergistic, detectible as 0.6 cGy making mixed ion more potent. Candidates for bystander transmission are microRNAs (miRNAs) and analysis miRNA-seq data from irradiated mice shows that would in theory, be downregulated. Further three previously identified miRNAs showed downregulation their targets associated with confirmed involvement pathways increased health risks cardiovascular disease. Finally, synthetic molecules (Antagomirs) designed inhibit predicted were successfully used reverse angiogenesis.