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Multi-omic Analysis of Non-human Primate Heart after Partial-body Radiation with Minimal Bone Marrow Sparing.
Health Physics ( IF 2.2 ) Pub Date : 2021-9-22 , DOI: 10.1097/hp.0000000000001478
Stephanie Zalesak-Kravec 1 , Weiliang Huang 1 , Pengcheng Wang 1 , Jianshi Yu 1 , Tian Liu 1 , Amy E Defnet 1 , Alexander R Moise 2 , Ann M Farese 3 , Thomas J MacVittie 3 , Maureen A Kane 1
Affiliation  

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.

中文翻译:

对非人类灵长类动物心脏进行局部放疗后保留最少骨髓的多组学分析。

高剂量辐射暴露会导致造血和胃肠道急性辐射综合征,随后急性辐射暴露会产生延迟效应,包括心脏、肾脏和肺等多个器官。在这里,我们试图通过测定心脏中的差异蛋白和代谢物表达来进一步描述辐射引起的心脏损伤的自然史。我们对非人类灵长类动物的左心室和右心室的蛋白质组和代谢组进行了定量分析,在 3 周的时间段内进行 12 Gy 局部身体照射,保留 2.5% 骨髓。全球蛋白质组分析鉴定出超过 2,200 种独特蛋白质,其中左心室和右心室分别有 220 种和 286 种蛋白质,与基线水平相比,在至少三个时间点显示出显着反应。高通量靶向代谢组学总共分析了 229 种代谢物和代谢物组合,其中左心室和右心室分别有 18 种和 22 种代谢物组合,与基线水平相比显示出显着的反应。对代谢组学和蛋白质组学数据进行的生物信息分析显示,与炎症、能量代谢和心肌重塑相关的通路失调。此外,我们观察到类视黄醇稳态通路的失调,包括辐射后视黄酸(维生素 A 的活性代谢物)的显着下降。确定了左心室和右心室在辐射引起的损伤病理学方面的显着差异。这项多组学研究描述了暴露于 PBI 且骨髓保留最少的 NHP 中辐射引起的心脏损伤的自然史和分子机制。
更新日期:2021-09-22
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