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Giacinto O, Pelliccia F, Minati A, De Crescenzo F, Garo ML, Chello M, Lusini M. Cosmic Radiations and the Cardiovascular System: A Narrative Review. Cardiol Rev 2024; 32:433-439. [PMID: 36728769 DOI: 10.1097/crd.0000000000000521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
In recent times, space flights receive continued interest. Humankind's next two goals are to return to the Moon and, a few years later, to land on the surface of Mars. Although technology will improve enough to enable long voyages, there are still some unresolved questions about the effects of the space environment on human health, including the effects of such long voyages on organs. Specifically, there is no information on the effects of radiation in space on the human cardiovascular system. To better understand the adaptation of the cardiovascular system to radiation exposure, the physical properties of radiation and the cellular and molecular mechanisms underlying tissue changes are essential. To this end, this article aims to provide an overview of the effects of radiation on the cardiovascular system by analyzing the physical properties of radiation and their relationship to cellular and molecular mechanisms and potential changes. Each type of radiation triggers different responses in the cardiovascular system. Radiation plays a relevant role in altering endothelial function and arterial wall stiffness by inducing vascular changes that accelerate atherosclerosis and affect endothelial adhesiveness. Clinical studies have shown that vascular changes due to radiation depend on the delayed manifestations of early radiation damage. To reduce the effects of radiation in space, some pharmacological treatments that seem to be able to counteract oxidative stress during flight are being used. At the same time, new shielding systems that can reduce or eliminate radiation exposure must be developed. Future studies should aim to replicate flights in the deep space environment to study in more detail the harmful effects of radiation on the whole cardiovascular system.
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Affiliation(s)
- Omar Giacinto
- From the Università Campus Bio-medico di Roma, UOC di Cardiochirurgia, Rome, Italy
| | | | | | | | - Maria Luisa Garo
- From the Università Campus Bio-medico di Roma, UOC di Cardiochirurgia, Rome, Italy
| | - Massimo Chello
- From the Università Campus Bio-medico di Roma, UOC di Cardiochirurgia, Rome, Italy
| | - Mario Lusini
- From the Università Campus Bio-medico di Roma, UOC di Cardiochirurgia, Rome, Italy
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2
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Wu T, Pelus LM, Plett PA, Sampson CH, Chua HL, Fisher A, Feng H, Liu L, Li H, Ortiz M, Chittajallu S, Luo Q, Bhatwadekar AD, Meyer TB, Zhang X, Zhou D, Fischer KD, McKinzie DL, Miller SJ, Orschell CM. Further Characterization of Multi-Organ DEARE and Protection by 16,16 Dimethyl Prostaglandin E2 in a Mouse Model of the Hematopoietic Acute Radiation Syndrome. Radiat Res 2023; 199:468-489. [PMID: 37014943 PMCID: PMC10278147 DOI: 10.1667/rade-22-00208.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/15/2023] [Indexed: 04/06/2023]
Abstract
Survivors of acute radiation exposure suffer from the delayed effects of acute radiation exposure (DEARE), a chronic condition affecting multiple organs, including lung, kidney, heart, gastrointestinal tract, eyes, and brain, and often causing cancer. While effective medical countermeasures (MCM) for the hematopoietic-acute radiation syndrome (H-ARS) have been identified and approved by the FDA, development of MCM for DEARE has not yet been successful. We previously documented residual bone marrow damage (RBMD) and progressive renal and cardiovascular DEARE in murine survivors of H-ARS, and significant survival efficacy of 16,16-dimethyl prostaglandin E2 (dmPGE2) given as a radioprotectant or radiomitigator for H-ARS. We now describe additional DEARE (physiological and neural function, progressive fur graying, ocular inflammation, and malignancy) developing after sub-threshold doses in our H-ARS model, and detailed analysis of the effects of dmPGE2 administered before (PGE-pre) or after (PGE-post) lethal total-body irradiation (TBI) on these DEARE. Administration of PGE-pre normalized the twofold reduction of white blood cells (WBC) and lymphocytes seen in vehicle-treated survivors (Veh), and increased the number of bone marrow (BM) cells, splenocytes, thymocytes, and phenotypically defined hematopoietic progenitor cells (HPC) and hematopoietic stem cells (HSC) to levels equivalent to those in non-irradiated age-matched controls. PGE-pre significantly protected HPC colony formation ex vivo by >twofold, long term-HSC in vivo engraftment potential up to ninefold, and significantly blunted TBI-induced myeloid skewing. Secondary transplantation documented continued production of LT-HSC with normal lineage differentiation. PGE-pre reduced development of DEARE cardiovascular pathologies and renal damage; prevented coronary artery rarefication, blunted progressive loss of coronary artery endothelia, reduced inflammation and coronary early senescence, and blunted radiation-induced increase in blood urea nitrogen (BUN). Ocular monocytes were significantly lower in PGE-pre mice, as was TBI-induced fur graying. Increased body weight and decreased frailty in male mice, and reduced incidence of thymic lymphoma were documented in PGE-pre mice. In assays measuring behavioral and cognitive functions, PGE-pre reduced anxiety in females, significantly blunted shock flinch response, and increased exploratory behavior in males. No effect of TBI was observed on memory in any group. PGE-post, despite significantly increasing 30-day survival in H-ARS and WBC and hematopoietic recovery, was not effective in reducing TBI-induced RBMD or any other DEARE. In summary, dmPGE2 administered as an H-ARS MCM before lethal TBI significantly increased 30-day survival and ameliorated RBMD and multi-organ and cognitive/behavioral DEARE to at least 12 months after TBI, whereas given after TBI, dmPGE2 enhances survival from H-ARS but has little impact on RBMD or other DEARE.
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Affiliation(s)
- Tong Wu
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Louis M. Pelus
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - P. Artur Plett
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Carol H. Sampson
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Hui Lin Chua
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Alexa Fisher
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Hailin Feng
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Liqiong Liu
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Hongge Li
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Miguel Ortiz
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Supriya Chittajallu
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Qianyi Luo
- Department of Ophthalmology, and Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Ashay D. Bhatwadekar
- Department of Ophthalmology, and Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Timothy B. Meyer
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Xin Zhang
- Department of Pharmacodynamics, University of Florida, Gainesville, Florida 32611
| | - Daohong Zhou
- Department of Pharmacodynamics, University of Florida, Gainesville, Florida 32611
| | - Kathryn D. Fischer
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - David L. McKinzie
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Steven J. Miller
- Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202
| | - Christie M. Orschell
- Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202
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Huff JL, Plante I, Blattnig SR, Norman RB, Little MP, Khera A, Simonsen LC, Patel ZS. Cardiovascular Disease Risk Modeling for Astronauts: Making the Leap From Earth to Space. Front Cardiovasc Med 2022; 9:873597. [PMID: 35665268 PMCID: PMC9161032 DOI: 10.3389/fcvm.2022.873597] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 04/26/2022] [Indexed: 11/24/2022] Open
Abstract
NASA has recently completed several long-duration missions to the International Space Station and is solidifying plans to return to the Moon, with an eye toward Mars and beyond. As NASA pushes the boundaries of human space exploration, the hazards of spaceflight, including space radiation, levy an increasing burden on astronaut health and performance. The cardiovascular system may be especially vulnerable due to the combined impacts of space radiation exposure, lack of gravity, and other spaceflight hazards. On Earth, the risk for cardiovascular disease (CVD) following moderate to high radiation doses is well-established from clinical, environmental, and occupational exposures (largely from gamma- and x-rays). Less is known about CVD risks associated with high-energy charged ions found in space and increasingly used in radiotherapy applications on Earth, making this a critical area of investigation for occupational radiation protection. Assessing CVD risk is complicated by its multifactorial nature, where an individual's risk is strongly influenced by factors such as family history, blood pressure, and lipid profiles. These known risk factors provide the basis for development of a variety of clinical risk prediction models (CPMs) that inform the likelihood of medical outcomes over a defined period. These tools improve clinical decision-making, personalize care, and support primary prevention of CVD. They may also be useful for individualizing risk estimates for CVD following radiation exposure both in the clinic and in space. In this review, we summarize unique aspects of radiation risk assessment for astronauts, and we evaluate the most widely used CVD CPMs for their use in NASA radiation risk assessment applications. We describe a comprehensive dual-use risk assessment framework that supports both clinical care and operational management of space radiation health risks using quantitative metrics. This approach is a first step in using personalized medicine for radiation risk assessment to support safe and productive spaceflight and long-term quality of life for NASA astronauts.
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Affiliation(s)
- Janice L. Huff
- National Aeronautics and Space Administration, Langley Research Center, Hampton, VA, United States
- *Correspondence: Janice L. Huff
| | - Ianik Plante
- KBR, Houston, TX, United States
- National Aeronautics and Space Administration, Johnson Space Center, Houston, TX, United States
| | - Steve R. Blattnig
- National Aeronautics and Space Administration, Langley Research Center, Hampton, VA, United States
| | - Ryan B. Norman
- National Aeronautics and Space Administration, Langley Research Center, Hampton, VA, United States
| | - Mark P. Little
- Division of Cancer Epidemiology and Genetics, Department of Health and Human Services (DHHS), Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, United States
| | - Amit Khera
- Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Lisa C. Simonsen
- National Aeronautics and Space Administration, NASA Headquarters, Washington, DC, United States
| | - Zarana S. Patel
- KBR, Houston, TX, United States
- National Aeronautics and Space Administration, Johnson Space Center, Houston, TX, United States
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Bishawi M, Lee FH, Abraham DM, Glass C, Blocker SJ, Cox DJ, Brown ZD, Rockman HA, Mao L, Slaba TC, Dewhirst MW, Truskey GA, Bowles DE. Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure. iScience 2022; 25:104086. [PMID: 35378858 PMCID: PMC8976132 DOI: 10.1016/j.isci.2022.104086] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 01/16/2022] [Accepted: 03/11/2022] [Indexed: 12/27/2022] Open
Abstract
The complex and inaccessible space radiation environment poses an unresolved risk to astronaut cardiovascular health during long-term space exploration missions. To model this risk, healthy male c57BL/6 mice aged six months (corresponding to an astronaut of 34 years) were exposed to simplified galactic cosmic ray (GCR5-ion; 5-ion sim) irradiation at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratories (BNL). Multi-modal cardiovascular functional assessments performed longitudinally and terminally revealed significant impairment in cardiac function in mice exposed to GCR5-ion compared to unirradiated controls, gamma irradiation, or single mono-energetic ions (56Fe or 16O). GCR5-ion-treated mice exhibited increased arterial elastance likely mediated by disruption of elastin fibers. This study suggests that a single exposure to GCR5-ion is associated with deterioration in cardiac structure and function that becomes apparent long after exposure, likely associated with increased morbidity and mortality. These findings represent important health considerations when preparing for successful space exploration.
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Affiliation(s)
- Muath Bishawi
- Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, MRSB1 Rm. 421b, 203 Research Drive, Durham, NC 27710, USA
- Department of Biomedical Engineering, Pratt School of Engineering, Durham, NC 27708, USA
| | - Franklin H. Lee
- Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, MRSB1 Rm. 421b, 203 Research Drive, Durham, NC 27710, USA
| | - Dennis M. Abraham
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
| | - Carolyn Glass
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
| | | | - Daniel J. Cox
- Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, MRSB1 Rm. 421b, 203 Research Drive, Durham, NC 27710, USA
| | - Zachary D. Brown
- Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, MRSB1 Rm. 421b, 203 Research Drive, Durham, NC 27710, USA
| | - Howard A. Rockman
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
| | - Lan Mao
- Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA
| | - Tony C. Slaba
- NASA Langley Research Center, Hampton, VA 23681, USA
| | - Mark W. Dewhirst
- Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA
| | - George A. Truskey
- Department of Biomedical Engineering, Pratt School of Engineering, Durham, NC 27708, USA
| | - Dawn E. Bowles
- Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, MRSB1 Rm. 421b, 203 Research Drive, Durham, NC 27710, USA
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Nemec-Bakk AS, Sridharan V, Landes RD, Singh P, Cao M, Seawright JW, Liu X, Zheng G, Dominic P, Pathak R, Boerma M. Mitigation of late cardiovascular effects of oxygen ion radiation by γ-tocotrienol in a mouse model. LIFE SCIENCES IN SPACE RESEARCH 2021; 31:43-50. [PMID: 34689949 PMCID: PMC8548672 DOI: 10.1016/j.lssr.2021.07.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/02/2021] [Accepted: 07/29/2021] [Indexed: 05/14/2023]
Abstract
PURPOSE While there is concern about degenerative tissue effects of exposure to space radiation during deep-space missions, there are no pharmacological countermeasures against these adverse effects. γ-Tocotrienol (GT3) is a natural form of vitamin E that has anti-oxidant properties, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. The purpose of this study was to test whether GT3 could mitigate cardiovascular effects of oxygen ion (16O) irradiation in a mouse model. MATERIALS AND METHODS Male C57BL/6 J mice were exposed to whole-body 16O (600 MeV/n) irradiation (0.26-0.33 Gy/min) at doses of 0 or 0.25 Gy at 6 months of age and were followed up to 9 months after irradiation. Animals were administered GT3 (50 mg/kg/day s.c.) or vehicle, on Monday - Friday starting on day 3 after irradiation for a total of 16 administrations. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters. Cardiac tissue remodeling and inflammatory infiltration were assessed with histology and immunoblot analysis at 2 weeks, 3 and 9 months after radiation. RESULTS GT3 mitigated the effects of 16O radiation on cardiac function, the expression of a collagen type III peptide, and markers of mast cells, T-cells and monocytes/macrophages in the left ventricle. CONCLUSIONS GT3 may be a potential countermeasure against late degenerative tissue effects of high-linear energy transfer radiation in the heart.
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Affiliation(s)
- Ashley S Nemec-Bakk
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
| | - Vijayalakshmi Sridharan
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Reid D Landes
- Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Preeti Singh
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Maohua Cao
- College of Dentistry, Texas A&M University, Dallas TX, USA
| | | | - Xingui Liu
- Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA
| | - Guangrong Zheng
- Department of Medicinal Chemistry, University of Florida, Gainesville, FL, USA
| | - Paari Dominic
- Department of Medicine and Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | - Rupak Pathak
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Marjan Boerma
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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Chatterjee S, Pietrofesa RA, Park K, Tao JQ, Carabe-Fernandez A, Berman AT, Koumenis C, Sielecki T, Christofidou-Solomidou M. LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks. Int J Mol Sci 2019; 20:ijms20010176. [PMID: 30621290 PMCID: PMC6337675 DOI: 10.3390/ijms20010176] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 12/24/2018] [Accepted: 12/25/2018] [Indexed: 12/29/2022] Open
Abstract
Updated measurements of charged particle fluxes during the transit from Earth to Mars as well as on site measurements by Curiosity of Martian surface radiation fluxes identified potential health hazards associated with radiation exposure for human space missions. Designing mitigation strategies of radiation risks to astronauts is critical. We investigated radiation-induced endothelial cell damage and its mitigation by LGM2605, a radioprotector with antioxidant and free radical scavenging properties. We used an in vitro model of lung vascular networks (flow-adapted endothelial cells; FAECs), exposed to gamma rays, low/higher linear energy transfer (LET) protons (3⁻4 or 8⁻10 keV/µm, respectively), and mixed field radiation sources (gamma and protons), given at mission-relevant doses (0.25 gray (Gy)⁻1 Gy). We evaluated endothelial inflammatory phenotype, NLRP3 inflammasome activation, and oxidative cell injury. LGM2605 (100 µM) was added 30 min post radiation exposure and gene expression changes evaluated 24 h later. Radiation induced a robust increase in mRNA levels of antioxidant enzymes post 0.25 Gy and 0.5 Gy gamma radiation, which was significantly decreased by LGM2605. Intercellular cell adhesion molecule-1 (ICAM-1) and NOD-like receptor protein 3 (NLRP3) induction by individual or mixed-field exposures were also significantly blunted by LGM2605. We conclude that LGM2605 is a likely candidate to reduce tissue damage from space-relevant radiation exposure.
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Affiliation(s)
- Shampa Chatterjee
- Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Ralph A Pietrofesa
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Kyewon Park
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Jian-Qin Tao
- Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Alejandro Carabe-Fernandez
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Abigail T Berman
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | - Constantinos Koumenis
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
| | | | - Melpo Christofidou-Solomidou
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
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Ramadan SS, Sridharan V, Koturbash I, Miousse IR, Hauer-Jensen M, Nelson GA, Boerma M. A priming dose of protons alters the early cardiac cellular and molecular response to (56)Fe irradiation. LIFE SCIENCES IN SPACE RESEARCH 2016; 8:8-13. [PMID: 26948008 PMCID: PMC4782196 DOI: 10.1016/j.lssr.2015.12.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Revised: 10/28/2015] [Accepted: 12/08/2015] [Indexed: 05/07/2023]
Abstract
PURPOSE Recent evidence suggests that the heart may be injured by ionizing radiation at lower doses than was previously thought. This raises concerns about the cardiovascular risks from exposure to radiation during space travel. Since space travel is associated with exposure to both protons from solar particle events and heavy ions from galactic cosmic rays, we here examined the effects of a "priming" dose of protons on the cardiac cellular and molecular response to a "challenge" dose of (56)Fe in a mouse model. METHODS Male C57BL/6 mice at 10 weeks of age were exposed to sham-irradiation, 0.1 Gy of protons (150 MeV), 0.5 Gy of (56)Fe (600 MeV/n), or 0.1 Gy of protons 24 hours prior to 0.5 Gy of (56)Fe. Hearts were obtained at 7 days post-irradiation and western-blots were used to determine protein markers of cardiac remodeling, inflammatory infiltration, and cell death. RESULTS Exposure to (56)Fe caused an increase in expression of α-smooth muscle cell actin, collagen type III, the inflammatory cell markers mast cell tryptase, CD2 and CD68, the endothelial glycoprotein thrombomodulin, and cleaved caspase 3. Of all proteins investigated, protons at a dose of 0.1 Gy induced a small increase only in cleaved caspase 3 levels. On the other hand, exposure to protons 24 hours before (56)Fe prevented all of the responses to (56)Fe. CONCLUSIONS This study shows that a low dose of protons may prime the heart to respond differently to a subsequent challenge dose of heavy ions. Further investigation is required to identify responses at additional time points, consequences for cardiac function, threshold dose levels, and mechanisms by which a proton priming dose may alter the response to heavy ions.
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Affiliation(s)
- Samy S Ramadan
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Vijayalakshmi Sridharan
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Igor Koturbash
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Isabelle R Miousse
- Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Martin Hauer-Jensen
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
| | - Gregory A Nelson
- Departments of Basic Sciences and Radiation Medicine, Loma Linda University, Loma Linda, CA 92354, USA
| | - Marjan Boerma
- Division of Radiation Health, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
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8
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Boerma M, Nelson GA, Sridharan V, Mao XW, Koturbash I, Hauer-Jensen M. Space radiation and cardiovascular disease risk. World J Cardiol 2015; 7:882-888. [PMID: 26730293 PMCID: PMC4691814 DOI: 10.4330/wjc.v7.i12.882] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 08/18/2015] [Accepted: 10/08/2015] [Indexed: 02/06/2023] Open
Abstract
Future long-distance space missions will be associated with significant exposures to ionizing radiation, and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Ground-based studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses, appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk, and several other studies are ongoing. Moreover, astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation, and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined, the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.
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Laiakis EC, Strassburg K, Bogumil R, Lai S, Vreeken RJ, Hankemeier T, Langridge J, Plumb RS, Fornace AJ, Astarita G. Metabolic phenotyping reveals a lipid mediator response to ionizing radiation. J Proteome Res 2014; 13:4143-54. [PMID: 25126707 PMCID: PMC4156265 DOI: 10.1021/pr5005295] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to γ radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to γ radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine.
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Affiliation(s)
- Evagelia C Laiakis
- Department of Biochemistry and Molecular & Cellular Biology, Georgetown University , Washington DC 20057, United States
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