Application of radiation omics in the development of adverse outcome pathway networks: an example of radiation-induced cardiovascular disease

Research output: Contribution to journalArticlepeer-review

Authors

  • Omid Azimzadeh
  • Simone Moertl
  • Raghda Ramadan
  • Bjorn Baselet
  • Evagelia C. Laiakis
  • Sebastian Soji
  • Danielle Beaton
  • Jaana M. Hartikainen
  • Jan Christian Kaiser
  • Afshin Beheshti
  • Sisko Salomaa
  • Aditya Chauhan
  • Nobuvuki Hamada

Institutes & Expert groups

  • Bfs - Bundesamt Für Strahlenschutz - Federal Office for Radiation Protection
  • Georgetown University
  • CNL - Canadian Nuclear Laboratories
  • University of Eastern Finland
  • ERHSD - Environmental and Radiation and Health Sciences Directorate, Health Canada
  • HMGU - Helmholtz Zentrum München - German Research Center for Environmental Health
  • NASA - Ames Research Center
  • STUK - Radiation and Nuclear Safety Authority
  • CRIEPI - Central Research Institute of Electric Power Industry

Documents & links

Abstract

Background

Epidemiological studies have indicated that exposure of the heart to doses of ionizing radiation as low as 0.5 Gy increases the risk of cardiac morbidity and mortality with a latency period of decades. The damaging effects of radiation to myocardial and endothelial structures and functions have been confirmed radiobiologically at high dose, but much less are known at low dose. Integration of radiation biology and epidemiology data is a recommended approach to improve the radiation risk assessment process. The adverse outcome pathway (AOP) framework offers a comprehensive tool to compile and translate mechanistic information into pathological endpoints which may be relevant for risk assessment at the different levels of a biological system. Omics technologies enable the generation of large volumes of biological data at various levels of complexity, from molecular pathways to functional organisms. Given the quality and quantity of available data across levels of biology, omics data can be attractive sources of information for use within the AOP framework. It is anticipated that radiation omics studies could improve our understanding of the molecular mechanisms behind the adverse effects of radiation on the cardiovascular system. In this review, we explored the available omics studies on radiation-induced cardiovascular disease (CVD) and their applicability to the proposed AOP for CVD.
Results
The results of 80 omics studies published on radiation-induced CVD over the past 20 years have been discussed in the context of the AOP of CVD proposed by Chauhan et al. Most of the available omics data on radiation-induced CVD are from proteomics, transcriptomics, and metabolomics, whereas few datasets were available from epigenomics and multi-omics. The omics data presented here show great promise in providing information for several key events (KEs) of the proposed AOP of CVD, particularly oxidative stress, alterations of energy metabolism, extracellular matrix (ECM), and vascular remodeling.
Conclusions
The omics data presented here shows promise to inform the various levels of the proposed AOP of CVD. However, the data highlight the urgent need of designing omics studies to address the knowledge gap concerning different radiation scenarios, time after exposure, and experimental models. This review presents the evidence to build a qualitative omics-informed AOP and provides views on the potential benefits and challenges in using omics data to assess risk-related outcomes.

Details

Original languageEnglish
Article number2110325
Pages (from-to)1-31
Number of pages31
JournalInternational Journal of Radiation Biology
DOIs
Publication statusPublished - 24 Aug 2022

Keywords

  • Ionizing radiation, Cardiovascular disease, Adverse outcome pathway, Omics, Genomics, Transcriptomics, miRNA, Ipigenomics, Proteomics, Secretome, Extracellular, Vesicles, Metabolomics, Lipodomics, Biofluid, Multi-omics, Systems biology, Modeling, Risk assessment, Biologically based dose-response

ID: 7938595