2017
DOI: 10.1667/rr14667.1
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Different Sequences of Fractionated Low-Dose Proton and Single Iron-Radiation-Induced Divergent Biological Responses in the Heart

Abstract: Deep-space travel presents risks of exposure to ionizing radiation composed of a spectrum of low-fluence protons (H) and high-charge and energy (HZE) iron nuclei (e.g., Fe). When exposed to galactic cosmic rays, each cell in the body may be traversed byH every 3-4 days and HZE nuclei every 3-4 months. The effects of low-dose sequential fractionated H or HZE on the heart are unknown. In this animal model of simulated ionizing radiation, middle-aged (8-9 months old) male C57BL/6NT mice were exposed to radiation … Show more

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Cited by 28 publications
(43 citation statements)
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“…It is recognized that unperturbed, native hematopoiesis and postmyeloablation hematopoiesis represent significantly different physiologies of blood development (30,31). In addition, radiation conditioning directly damages cardiovascular tissues (18) and, as shown here, leads to significantly accelerated replacement of cardiac-resident macrophages by donor bone marrow-derived cells that parallels the rapid replacement of cell populations in the bone marrow. Emerging evidence shows that resident cardiac macrophages exhibit broad diversity with distinct properties from the circulating monocyte-derived macrophages and that some fractions of resident cardiac macrophages exert regenerative and protective functions in models of injury (32,33).…”
Section: Discussionmentioning
confidence: 71%
See 1 more Smart Citation
“…It is recognized that unperturbed, native hematopoiesis and postmyeloablation hematopoiesis represent significantly different physiologies of blood development (30,31). In addition, radiation conditioning directly damages cardiovascular tissues (18) and, as shown here, leads to significantly accelerated replacement of cardiac-resident macrophages by donor bone marrow-derived cells that parallels the rapid replacement of cell populations in the bone marrow. Emerging evidence shows that resident cardiac macrophages exhibit broad diversity with distinct properties from the circulating monocyte-derived macrophages and that some fractions of resident cardiac macrophages exert regenerative and protective functions in models of injury (32,33).…”
Section: Discussionmentioning
confidence: 71%
“…These competitive BMT models serve to minimize the confounding effects that these driver gene mutations exert in animal models, including elevated immune cell levels and systemic tissue inflammation, which are generally not features observed in individuals with clonal hematopoiesis. Regardless, these experimental systems have significant drawbacks in modeling human clonal hematopoiesis because of the systemic effects of irradiation on cardiovascular tissues (18), damage to the bone marrow niche, (19) and lineage bias due to the differentiation of a small fraction of dominant HSC clones (20). In view of these issues, we investigated a model of murine clonal hematopoiesis that involves the adoptive transfer of unfractionated bone marrow cells to mice that have not been preconditioned by a myeloablative strategy.…”
Section: Introductionmentioning
confidence: 99%
“…To develop better models of clonal haematopoiesis, it is desirable to avoid the irradiation procedures that destroy the bone marrow niche and damage tissues throughout the body [46][47][48][49]. In avoiding myeloablative strategies, clonal haematopoiesis experiments can also be conducted under conditions that more faithfully mimic the regulatory mechanisms associated with native haematopoiesis [50,51].…”
Section: Mechanistic Links Between Clonal Haematopoiesis and Cardiovamentioning
confidence: 99%
“…Prior studies have reported oxidative stress in the central nervous system of mice due to exposure to low-LET radiation at doses <1 Gy in chronic low dose rates [12]. Other laboratories have shown behavioral deficiencies and increased cardiovascular risk associated with low dose 1 H and HZE radiation [13,14]. Though the majority of reports on health effects of γ-radiation is in the context of medical exposure, metabolic alterations that are dose dependent and across various time points have also been reported [15,16].…”
Section: Introductionmentioning
confidence: 99%