Open AccessMulti-omic Analysis of Non-human Primate Heart after Partial-body Radiation with Minimal Bone Marrow Sparing
Author(s) -
Stephanie ZalesakKravec,
Weiliang Huang,
Pengcheng Wang,
Jianshi Yu,
Tian Liu,
Amy Defnet,
Alexander R. Moise,
Ann M. Farese,
Thomas J. MacVittie,
Maureen A. Kane
Publication year - 2021
Publication title -
health physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.357
H-Index - 73
eISSN - 1538-5159
pISSN - 0017-9078
DOI - 10.1097/hp.0000000000001478
Subject(s) - metabolome , bone marrow , metabolomics , metabolite , ionizing radiation , ventricle , haematopoiesis , medicine , pathology , biology , bioinformatics , microbiology and biotechnology , stem cell , irradiation , physics , nuclear physics
High-dose radiation exposure results in hematopoietic and gastrointestinal acute radiation syndromes followed by delayed effects of acute radiation exposure, which encompasses multiple organs, including heart, kidney, and lung. Here we sought to further characterize the natural history of radiation-induced heart injury via determination of differential protein and metabolite expression in the heart. We quantitatively profiled the proteome and metabolome of left and right ventricle from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Global proteome profiling identified more than 2,200 unique proteins, with 220 and 286 in the left and right ventricles, respectively, showing significant responses across at least three time points compared to baseline levels. High-throughput targeted metabolomics analyzed a total of 229 metabolites and metabolite combinations, with 18 and 22 in the left and right ventricles, respectively, showing significant responses compared to baseline levels. Bioinformatic analysis performed on metabolomic and proteomic data revealed pathways related to inflammation, energy metabolism, and myocardial remodeling were dysregulated. Additionally, we observed dysregulation of the retinoid homeostasis pathway, including significant post-radiation decreases in retinoic acid, an active metabolite of vitamin A. Significant differences between left and right ventricles in the pathology of radiation-induced injury were identified. This multi-omic study characterizes the natural history and molecular mechanisms of radiation-induced heart injury in NHP exposed to PBI with minimal bone marrow sparing.