Spaceflight removes the normal loading effects of gravity on the cardiovascular system and initiates 'ageing-like' deconditioning, including loss of physical fitness, arterial stiffening, and development of insulin resistance
Exposure to cosmic radiation during space travel might induce late cardiovascular disease
Whether a threshold radiation dose exists for adverse cardiovascular effects is still uncertain
Countermeasures to reduce the risk of spaceflight-associated, radiation-induced cardiovascular disease include maintenance of physical fitness, dietary and nutraceutical interventions, and radiation shielding
National space agencies and private corporations aim at an extended presence of humans in space in the medium to long term. Together with currently suboptimal technology, microgravity and cosmic rays raise health concerns about deep-space exploration missions. Both of these physical factors affect the cardiovascular system, whose gravity-dependence is pronounced. Heart and vascular function are, therefore, susceptible to substantial changes in weightlessness. The altered cardiovascular function in space causes physiological problems in the postflight period. A compromised cardiovascular system can be excessively vulnerable to space radiation, synergistically resulting in increased damage. The space radiation dose is significantly lower than in patients undergoing radiotherapy, in whom cardiac damage is well-documented following cancer therapy in the thoracic region. Nevertheless, epidemiological findings suggest an increased risk of late cardiovascular disease even with low doses of radiation. Moreover, the peculiar biological effectiveness of heavy ions in cosmic rays might increase this risk substantially. However, whether radiation-induced cardiovascular effects have a threshold at low doses is still unclear. The main countermeasures to mitigate the effect of the space environment on cardiac function are physical exercise, antioxidants, nutraceuticals, and radiation shielding.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
International Space Exploration Coordination Group (ISECG). The global exploration roadmap. (ISECG, 2013).
Cucinotta, F. A. & Durante, M. Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol. 7, 431–435 (2006).
Hughson, R. L. Recent findings in cardiovascular physiology with space travel. Respir. Physiol. Neurobiol. 169, S38–S41 (2009).
Benjamin, E. J. et al. Heart disease and stroke statistics — 2017 update: a report from the American heart association. Circulation 135, e146–e603 (2017).
Darby, S. C. et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N. Engl. J. Med. 368, 987–998 (2013).
Tapio, S. Pathology and biology of radiation-induced cardiac disease. J. Radiat. Res. 57, 439–448 (2016).
Després, J. P. Physical activity, sedentary behaviours, and cardiovascular health: when will cardiorespiratory fitness become a vital sign? Can. J. Cardiol. 32, 505–513 (2016).
Kozlovskaya, I. B. et al. Russian countermeasure systems for adverse effects of microgravity on long-duration ISS flights. Aerosp. Med. Hum. Perform. 86, A24–A31 (2015).
Petersen, N. et al. Exercise in space: the European Space Agency approach to in-flight exercise countermeasures for long-duration missions on ISS. Extrem. Physiol. Med. 5, 9 (2016).
Fraser, K. S., Greaves, D. K., Shoemaker, J. K., Blaber, A. P. & Hughson, R. L. Heart rate and daily physical activity with long-duration habitation of the International Space Station. Aviat. Space Environ. Med. 83, 577–584 (2012).
Owen, N., Healy, G. N., Matthews, C. E. & Dunstan, D. W. Too much sitting: the population health science of sedentary behavior. Exerc. Sport Sci. Rev. 38, 105–113 (2010).
Eckel, R. H. et al. 2013 AHA/ACC Guideline on lifestyle management to reduce cardiovascular risk. Circulation 129, S76–S99 (2014).
Stein, T. P. Weight, muscle and bone loss during space flight: another perspective. Eur. J. Appl. Physiol. 113, 2171–2181 (2013).
Smith, S. M., Zwart, S. R., Block, G., Rice, B. L. & Davis-Street, J. E. The nutritional status of astronauts is altered after long-term space flight aboard the International Space Station. J. Nutr. 135, 437–443 (2005).
Hughson, R. L. et al. Increased postflight carotid artery stiffness and inflight insulin resistance resulting from 6-mo spaceflight in male and female astronauts. Am. J. Physiol. Heart Circ. Physiol. 310, H628–H638 (2016).
Hargens, A. R. & Richardson, S. Cardiovascular adaptations, fluid shifts, and countermeasures related to space flight. Respir. Physiol. Neurobiol. 169, S30–S33 (2009).
Eckberg, D. L. et al. Human vagal baroreflex mechanisms in space. J. Physiol. 588, 1129–1138 (2010).
Hughson, R. L. et al. Cardiovascular regulation during long-duration spaceflights to the International Space Station. J. Appl. Physiol. 112, 719–727 (2012).
Norsk, P. et al. Vasorelaxation in Space. Hypertension 47, 69–73 (2006).
Blomqvist, C. G. & Stone, H. L. in Handbook of Physiology. The Cardiovascular System. Peripheral Circulation and Organ Blood Flow (eds Shepherd, J. T., Abboud, F. M. & Geiger, S. R.) 1025–1063 (American Physiological Society, 1983).
Lavie, C. J. et al. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ. Res. 117, 207–219 (2015).
Ade, C. J. et al. Prediction of Lunar- and Martian-based intra- and site-to-site task performance. Aerosp. Med. Hum. Perform. 87, 367–374 (2016).
Durante, M. & Cucinotta, F. A. Physical basis of radiation protection in space travel. Rev. Mod. Phys. 83, 1245–1281 (2011).
Zeitlin, C. et al. Measurements of energetic particle radiation in transit to Mars on the Mars Science Laboratory. Science 340, 1080–1084 (2013).
Kirsch, K. A., Baartz, F. J., Gunga, H. C. & Röcker, L. Fluid shifts into and out of superficial tissues under microgravity and terrestrial conditions. Clin. Investig. 71, 687–689 (1993).
Buckey, J. C. Jr et al. Central venous pressure in space. J. Appl. Physiol. 81, 19–25 (1996).
Leach, C. S. et al. Regulation of body fluid compartments during short-term spaceflight. J. Appl. Physiol. 81, 105–116 (1996).
Stein, T. P. & Gaprindashvili, T. Spaceflight and protein metabolism, with special reference to humans. Am. J. Clin. Nutr. 60, 806S–819S (1994).
Gharib, C. & Hughson, R. L. in Advances in Space Biology and Medicine Vol. 2 (ed. Bonting, S. L. ) 113–130 (JAI Press Inc., 1991).
Drummer, C., Gerzer, R., Baisch, F. & Heer, M. Body fluid regulation in μ-gravity differs from that on Earth: an overview. Pflugers Arch. 441, R66–R72 (2000).
Norsk, P. et al. Renal and endocrine responses in humans to isotonic saline infusion during microgravity. J. Appl. Physiol. 78, 2253–2259 (1995).
Alfrey, C. P., Udden, M. M., Leach-Huntoon, C., Driscoll, T. & Pickett, M. H. Control of red blood cell mass in spaceflight. J. Appl. Physiol. 81, 98–104 (1996).
Alfrey, C. P., Udden, M. M., Huntoon, C. L. & Driscoll, T. Destruction of newly released red blood cells in space flight. Med. Sci. Sports Exerc. 28, S42–S44 (1996).
Rizzo, A. M. et al. Effects of long-term space flight on erythrocytes and oxidative stress of rodents. PLoS ONE 7, e32361 (2012).
Norsk, P., Asmar, A., Damgaard, M. & Christensen, N. J. Fluid shifts, vasodilatation and ambulatory blood pressure reduction during long duration spaceflight. J. Physiol. 593, 573–584 (2015).
Shaldon, S. & Vienken, J. Beyond the current paradigm: recent advances in the understanding of sodium handling. Semin. Dial. 22, 253–255 (2009).
Rodan, A. R., Cheng, C. J. & Huang, C. L. Recent advances in distal tubular potassium handling. Am. J. Physiol. Renal Physiol. 300, F821–F827 (2011).
Fritsch-Yelle, J. M., Charles, J. B., Jones, M. M., Beightol, L. A. & Eckberg, D. L. Spaceflight alters autonomic regulation of arterial pressure in humans. J. Appl. Physiol. 77, 1776–1783 (1994).
Ertl, A. C. et al. Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space. J. Physiol. 538, 321–329 (2002).
Arbeille, P. et al. Adaptation of the left heart, cerebral and femoral arteries, and jugular and femoral veins during short- and long-term head-down tilt and spaceflights. Eur. J. Appl. Physiol. 86, 157–168 (2001).
Gaffney, F. A. et al. Cardiovascular deconditioning produced by 20 hours of bedrest with head-down tilt (−5°) in middle-aged healthy men. Am. J. Cardiol. 56, 634–638 (1985).
Meck, J. V. et al. Mechanisms of postspaceflight orthostatic hypotension: low β1-adrenergic receptor responses before flight and central autonomic dysregulation postflight. Am. J. Physiol. Heart Circ. Physiol. 286, H1486–H1495 (2004).
Meck, J. V., Reyes, C. J., Perez, S., Goldberger, A. L. & Ziegler, M. G. Marked exacerbation of orthostatic intolerance after long-versus short-duration spaceflight in veteran astronauts. Psychosom. Med. 63, 865–873 (2001).
Zuj, K. A. et al. Impaired cerebrovascular autoregulation and reduced CO2 reactivity after long duration spaceflight. Am. J. Physiol. Heart Circ. Physiol. 302, H2592–H2598 (2012).
Prisk, G. K. et al. Pulmonary diffusing capacity, capillary blood volume, and cardiac output during sustained microgravity. J. Appl. Physiol. 75, 15–26 (1993).
Norsk, P. & Christensen, N. J. The paradox of systemic vasodilatation and sympathetic nervous stimulation in space. Respir. Physiol. Neurobiol. 169, S26–S29 (2009).
Dorfman, T. A. et al. Cardiac atrophy in women following bed rest. J. Appl. Physiol. 103, 8–16 (2007).
Perhonen, M. A. et al. Cardiac atrophy after bed rest and spaceflight. J. Appl. Physiol. 91, 645–653 (2001).
Carrick-Ranson, G., Hastings, J. L., Bhella, P. S., Shibata, S. & Levine, B. D. The effect of exercise training on left ventricular relaxation and diastolic suction at rest and during orthostatic stress after bed rest. Exp. Physiol. 98, 501–513 (2013).
Dorfman, T. A. et al. Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting. J. Appl. Physiol. 104, 1037–1044 (2008).
Martin, D. S., South, D. A., Wood, M. L., Bungo, M. W. & Meck, J. V. Comparison of echocardiographic changes after short- and long-duration spaceflight. Aviat. Space Environ. Med. 73, 532–536 (2002).
Abdullah, S. M. et al. Effects of prolonged space flight on cardiac structure and function [abstract]. Circulation 128, A18672 (2013).
Watenpaugh, D. E. & Hargens, A. R. in Handbook of Physiology. Environmental Physiology (eds Fregley, M. J. & Blatteis, C M.) 631–674 (Oxford Univ. Press, 1996).
Levine, B. D. et al. Maximal exercise performance after adaptation to microgravity. J. Appl. Physiol. 81, 686–694 (1996).
Rummel, J. A., Sawin, C. F. & Michel, E. L. in Biomedical Results of Apollo (eds Johnston, R. S., Dietlein, L. F. & Berry, C. A.) 265–275 (National Aeronautics and Space Administration, 1975).
Trappe, T. et al. Cardiorespiratory responses to physical work during and following 17 days of bed rest and spaceflight. J. Appl. Physiol. 100, 951–957 (2006).
Fitts, R. H. et al. Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres. J. Physiol. 588, 3567–3592 (2010).
Trappe, S. et al. Exercise in space: human skeletal muscle after 6 months aboard the International Space Station. J. Appl. Physiol. 106, 1159–1168 (2009).
Moore, A. D., Lynn, P. A. & Feiveson, A. H. The first 10 years of aerobic exercise responses to long-duration ISS flights. Aerosp. Med. Hum. Perform. 86, A78–A86 (2015).
Moore, A. D. et al. Peak exercise oxygen uptake during and following long-duration spaceflight. J. Appl. Physiol. 117, 231–238 (2014).
Lorenz, M. W., Markus, H. S., Bots, M. L., Rosvall, M. & Sitzer, M. Prediction of clinical cardiovascular events with carotid intima-media thickness. Circulation 115, 459 (2007).
Arbeille, P., Achaibou, F., Fomina, G., Pottier, J. M. & Porcher, M. Regional blood flow in microgravity: adaptation and deconditioning. Med. Sci. Sports Exerc. 28, S70–S79 (1996).
Herault, S. et al. Cardiac, arterial and venous adaptation to weightlessness during 6-month MIR spaceflights with and without thigh cuffs (bracelets). EJAP 81, 384–390 (2000).
Wilkerson, M. K., Muller-Delp, J., Colleran, P. N. & Delp, M. D. Effects of hindlimb unloading on rat cerebral, splenic, and mesenteric resistance artery morphology. J. Appl. Physiol. 87, 2115–2121 (1999).
Zhang, L.-F. Vascular adaptation to microgravity: what have we learned? J. Appl. Physiol. 91, 2415–2430 (2001).
Arbeille, P., Provost, R. & Zuj, K. Carotid and femoral artery intima-media thickness during 6 months of spaceflight. Aerosp. Med. Hum. Perform. 87, 449–453 (2016).
Baevsky, R. M. et al. Autonomic cardiovascular and respiratory control during prolonged spaceflights aboard the International Space Station. J. Appl. Physiol. 103, 156–161 (2007).
Arbeille, P., Provost, R., Vincent, N. & Aubert, A. Adaptation of the main peripheral artery and vein to long term confinement (MARS 500). PLoS ONE 9, e83063 (2014).
Wang, G., Jacquet, L., Karamariti, E. & Xu, Q. Origin and differentiation of vascular smooth muscle cells. J. Physiol. 593, 3013–3030 (2015).
Avolio, A. et al. Regulation of arterial stiffness: cellular, molecular and neurogenic mechanisms. Artery Res. 5, 122–127 (2011).
Leach, C. S., Johnson, P. C. & Cintron, N. M. The endocrine system in space flight. Acta Astronaut. 17, 161–166 (1988).
Zieman, S. J., Melenovsky, V. & Kass, D. A. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler. Thromb. Vasc. Biol. 25, 932–943 (2005).
Tuday, E. C., Nyhan, D., Shoukas, A. A. & Berkowitz, D. E. Simulated microgravity-induced aortic remodeling. J. Appl. Physiol. 106, 2002–2008 (2009).
Zhang, R. et al. Blockade of AT1 receptor partially restores vasoreactivity, NOS expression, and superoxide levels in cerebral and carotid arteries of hindlimb unweighting rats. J. Appl. Physiol. 106, 251–258 (2009).
Taylor, C. R. et al. Spaceflight-induced alterations in cerebral artery vasoconstrictor, mechanical, and structural properties: implications for elevated cerebral perfusion and intracranial pressure. FASEB J. 27, 2282–2292 (2013).
Sofronova, S. I. et al. Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and mechanical properties in mice. J. Appl. Physiol. 118, 830–838 (2015).
Seals, D. R. Edward, F. Adolph Distinguished Lecture: the remarkable anti-aging effects of aerobic exercise on systemic arteries. J. Appl. Physiol. 117, 425–439 (2014).
Shi, Y. & Vanhoutte, P. M. Macro- and microvascular endothelial dysfunction in diabetes. J. Diabetes. 9, 434–449 (2017).
Bonnin, P. et al. Enhanced flow-dependent vasodilatation after bed rest, a possible mechanism for orthostatic intolerance in humans. Eur. J. Appl. Physiol. 85, 420–426 (2001).
Bleeker, M. W. P. et al. Vascular adaptation to deconditioning and the effect of an exercise countermeasure: results of the Berlin Bed Rest study. J. Appl. Physiol. 99, 1293–1300 (2005).
Platts, S. H. et al. Cardiovascular adaptations to long-duration head-down bed rest. Aviat. Space Environ. Med. 80, A29–A36 (2009).
van Duijnhoven, N. T. L. et al. Impact of bed rest on conduit artery remodeling: effect of exercise countermeasures. Hypertension 56, 240–246 (2010).
van Duijnhoven, N. T. L. et al. Resistive exercise versus resistive vibration exercise to counteract vascular adaptations to bed rest. J. Appl. Physiol. 108, 28–33 (2010).
Demiot, C. et al. WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. Am. J. Physiol. Heart Circ. Physiol. 293, H3159–H3164 (2007).
Zhang, R. et al. Increased vascular cell adhesion molecule-1 was associated with impaired endothelium-dependent relaxation of cerebral and carotid arteries in simulated microgravity rats. J. Physiol. Sci. 58, 67–73 (2008).
Soucy, K. et al. Single exposure to radiation produces early anti-angiogenic effects in mouse aorta. Radiat. Environ. Biophys. 49, 397–404 (2010).
Ghosh, P. et al. Effects of high-LET radiation exposure and hindlimb unloading on skeletal muscle resistance artery vasomotor properties and cancellous bone microarchitecture in mice. Radiat. Res. 185, 257–266 (2016).
Soucy, K. G. et al. Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta. J. Appl. Physiol. 108, 1250–1258 (2010).
Delp, M. D., Charvat, J. M., Limoli, C. L., Globus, R. K. & Ghosh, P. Apollo lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium. Sci. Rep. 6, 29901 (2016).
Darby, S. C. et al. Radiation-related heart disease: current knowledge and future prospects. Int. J. Radiat. Oncol. Biol. Phys. 76, 656–665 (2010).
Cutter, D. J. et al. Risk for valvular heart disease after treatment for Hodgkin lymphoma. J. Natl Cancer Inst. 107, 1–9 (2015).
Aleman, B. M. P. et al. Cardiovascular disease after cancer therapy. Eur. J. Cancer Suppl. 12, 18–28 (2014).
Cuomo, J. R., Sharma, G. K., Conger, P. D. & Weintraub, N. L. Novel concepts in radiation-induced cardiovascular disease. World J. Cardiol. 8, 504–519 (2016).
Boerma, M. et al. Space radiation and cardiovascular disease risk. World J. Cardiol. 7, 882–888 (2015).
Little, M. P. Radiation and circulatory disease. Mutat. Res. 770, 299–318 (2016).
Preston, D. L., Shimizu, Y., Pierce, D. A., Suyama, A. & Mabuchi, K. Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950–1997. Radiat. Res. 160, 381–407 (2003).
Shimizu, Y. et al. Radiation exposure and circulatory disease risk: Hiroshima and Nagasaki atomic bomb survivor data, 1950–2003. BMJ 340, b5349 (2010).
Azizova, T. V. et al. Cardiovascular diseases in the cohort of workers first employed at Mayak PA in 1948–1958. Radiat. Res. 174, 155–168 (2010).
Azizova, T. V., Grigorieva, E. S., Hunter, N., Pikulina, M. V. & Moseeva, M. B. Risk of mortality from circulatory diseases in Mayak workers cohort following occupational radiation exposure. J. Radiol. Prot. 35, 517–538 (2015).
Tran, V., Zablotska, L. B., Brenner, A. V. & Little, M. P. Radiation-associated circulatory disease mortality in a pooled analysis of 77,275 patients from the Massachusetts and Canadian tuberculosis fluoroscopy cohorts. Sci. Rep. 7, 44147 (2017).
Little, M. P. A review of non-cancer effects, especially circulatory and ocular diseases. Radiat. Environ. Biophys. 52, 435–449 (2013).
Kashcheev, V. V. et al. Radiation risk of cardiovascular diseases in the cohort of Russian emergency workers of the Chernobyl accident. Health Phys. 113, 23–29 (2017).
Cucinotta, F. A., Kim, M.-H. Y., Chappell, L. J. & Huff, J. L. How safe is safe enough? Radiation risk for a human mission to Mars. PLoS ONE 8, e74988 (2013).
Durante, M. & Cucinotta, F. A. Heavy ion carcinogenesis and human space exploration. Nat. Rev. Cancer. 8, 465–472 (2008).
Cucinotta, F. A., Hamada, N. & Little, M. P. No evidence for an increase in circulatory disease mortality in astronauts following space radiation exposures. Life Sci. Space Res. 10, 53–56 (2016).
Ade, C. J., Broxterman, R. V., Charvat, J. M. & Barstow, T. J. Incidence rate of cardiovascular disease end points in the National Aeronautics and Space Administration astronaut corps. J. Am. Heart. Assoc. 6, e005564 (2017).
Yang, V. V., Stearner, S. P. & Tyler, S. A. Radiation-induced changes in the fine structure of the heart: comparison of fission neutrons and 60Co gamma rays in the mouse. Radiat. Res. 67, 344–360 (1976).
Yang, V. V., Stearner, S. P. & Ainsworth, E. J. Late ultrastructural changes in the mouse coronary arteries and aorta after fission neutron or 60Co gamma irradiation. Radiat. Res. 74, 436–456 (1978).
Stearner, S. P., Yang, V. V. & Devine, R. L. Cardiac injury in the aged mouse: comparative ultrastructural effects of fission spectrum neutrons and gamma rays. Radiat. Res. 78, 429–447 (1979).
Grabham, P., Hu, B., Sharma, P. & Geard, C. Effects of ionizing radiation on three-dimensional human vessel models: differential effects according to radiation quality and cellular development. Radiat. Res. 175, 21–28 (2011).
Grabham, P., Bigelow, A. & Geard, C. DNA damage foci formation and decline in two-dimensional monolayers and in three-dimensional human vessel models: differential effects according to radiation quality. Int. J. Radiat. Biol. 88, 493–500 (2012).
Grabham, P., Sharma, P., Bigelow, A. & Geard, C. Two distinct types of the inhibition of vasculogenesis by different species of charged particles. Vasc. Cell 5, 16 (2013).
Sanzari, J. K. et al. Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model. Life Sci. Space Res. 6, 21–28 (2015).
Yan, X. et al. Cardiovascular risks associated with low dose ionizing particle radiation. PLoS ONE 9, e110269 (2014).
Coleman, M. A. et al. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 309, H1947–H1963 (2015).
Koturbash, I. et al. Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart. Mutat. Res. 787, 43–53 (2016).
Impey, S. et al. Proton irradiation induces persistent and tissue-specific DNA methylation changes in the left ventricle and hippocampus. BMC Genomics. 17, 273 (2016).
Kundel, H. L. The effect of high-energy proton irradiation on the cardiovascular system of the rhesus monkey. Radiat. Res. 28, 529–537 (1966).
Helm, A., Lee, R., Durante, M. & Ritter, S. The influence of C-ions and X-rays on human umbilical vein endothelial cells. Front. Oncol. 6, 5 (2016).
Beck, M. et al. Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation. Int. J. Mol. Med. 34, 1124–1132 (2014).
Takahashi, Y. et al. Heavy ion irradiation inhibits in vitro angiogenesis even at sublethal dose. Cancer Res. 63, 4253–4257 (2003).
Gridley, D. S., Obenaus, A., Bateman, T. A. & Pecaut, M. J. Long-term changes in rat hematopoietic and other physiological systems after high-energy iron ion irradiation. Int. J. Radiat. Biol. 84, 549–559 (2008).
Soucy, K. G. et al. HZE 56Fe-ion irradiation induces endothelial dysfunction in rat aorta: role of xanthine oxidase. 176, 474–485 (2011).
Yang, V. V. & Ainsworth, E. J. Late effects of heavy charged particles on the fine structure of the mouse coronary artery. Radiat. Res. 91, 135–144 (1982).
Yu, T. et al. Iron-ion radiation accelerates atherosclerosis in apolipoprotein E-deficient mice. Radiat. Res. 175, 766–773 (2011).
Kiyohara, H. et al. Radiation-induced ICAM-1 expression via TGF-β1 pathway on human umbilical vein endothelial cells; comparison between X-ray and carbon-ion beam irradiation. J. Radiat. Res. 52, 287–292 (2011).
Tungjai, M., Whorton, E. B. & Rithidech, K. N. Persistence of apoptosis and inflammatory responses in the heart and bone marrow of mice following whole-body exposure to 28Silicon (28Si) ions. Radiat. Environ. Biophys. 52, 339–350 (2013).
Jeon, Y.-H., Kraus, S. G., Jowsey, T. & Glasgow, N. J. The experience of living with chronic heart failure: a narrative review of qualitative studies. BMC Health Serv. Res. 10, 1–9 (2010).
Baselet, B., Rombouts, C., Benotmane, A., Baatout, S. & Aerts, A. Cardiovascular diseases related to ionizing radiation: the risk of low-dose exposure (Review). Int. J. Mol. Med. 38, 1623–1641 (2016).
Libby, P. & Theroux, P. Pathophysiology of coronary artery disease. Circulation 111, 3481–3488 (2005).
Wong, N. D. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat. Rev. Cardiol. 11, 276–289 (2014).
Libby, P., Ridker, P. M. & Hansson, G. K. Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317–325 (2011).
Tabas, I., García-Cardeña, G. & Owens, G. K. Recent insights into the cellular biology of atherosclerosis. J. Cell Biol. 209, 13–22 (2015).
Bhattacharya, S. & Asaithamby, A. Ionizing radiation and heart risks. Semin. Cell Dev. Biol. 58, 14–25 (2016).
Hendry, J. H. et al. Radiation-induced cardiovascular injury. Radiat. Environ. Biophys. 47, 189–193 (2008).
Little, M. P. et al. Review and meta-analysis of epidemiological associations between low/moderate doses of ionizing radiation and circulatory disease risks, and their possible mechanisms. Radiat. Environ. Biophys. 49, 139–153 (2009).
Mancuso, M. et al. Acceleration of atherogenesis in ApoE−/− mice exposed to acute or low-dose-rate ionizing radiation. Oncotarget 6, 31263–31271 (2015).
Tribble, D. L., Barcellos-Hoff, M. H., Chu, B. M. & Gong, E. L. Ionizing radiation accelerates aortic lesion formation in fat-fed mice via SOD-inhibitable processes. Vasc. Biol. 19, 1387–1392 (1999).
Mitchel, R. E. J. et al. Low-dose radiation exposure and atherosclerosis in ApoE−/− mice. Radiat. Res. 175, 665–676 (2011).
Mitchel, R. E. J. et al. Low-dose radiation exposure and protection against atherosclerosis in ApoE−/− mice: the influence of P53 heterozygosity. Radiat. Res. 179, 190–199 (2013).
Boerma, M. & Hauer-Jensen, M. Preclinical research into basic mechanisms of radiation-induced heart disease. Cardiol. Res. Pract. 2011, 858262 (2011).
Warrington, J. P. et al. Whole brain radiation-induced vascular cognitive impairment: mechanisms and implications. J. Vasc. Res. 50, 445–457 (2013).
Azimzadeh, O. et al. Rapid proteomic remodeling of cardiac tissue caused by total body ionizing radiation. Proteomics 11, 3299–3311 (2011).
Kim, J. H., Jenrow, K. A. & Brown, S. L. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat. Oncol. J. 32, 103–115 (2014).
Davidson, S. M. & Duchen, M. R. Endothelial mitochondria: contributing to vascular function and disease. Circ. Res. 100, 1128–1141 (2007).
Donato, A. J. et al. Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-κB. Circ. Res. 100, 1659–1666 (2007).
Barjaktarovic, Z. et al. Radiation-induced signaling results in mitochondrial impairment in mouse heart at 4 weeks after exposure to X-rays. PLoS ONE 6, e27811 (2011).
Lundberg, J. O., Gladwin, M. T. & Weitzberg, E. Strategies to increase nitric oxide signalling in cardiovascular disease. Nat. Rev. Drug Discov. 14, 623–641 (2015).
Azimzadeh, O. et al. PPAR alpha: a novel radiation target in locally exposed Mus musculus heart revealed by quantitative proteomics. J. Proteome Res. 12, 2700–2714 (2013).
Azimzadeh, O. et al. A dose-dependent perturbation in cardiac energy metabolism is linked to radiation-induced ischemic heart disease in Mayak nuclear workers. Oncotarget 8, 9067–9078 (2017).
Azimzadeh, O. et al. Integrative proteomics and targeted transcriptomics analyses in cardiac endothelial cells unravel mechanisms of long-term radiation-induced vascular dysfunction. J. Proteome Res. 14, 1203–1219 (2015).
Rousseau, M. et al. RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration. Biochem. Biophys. Res. Commun. 414, 750–755 (2011).
Jelonek, K. et al. Cardiac endothelial cells isolated from mouse heart — a novel model for radiobiology. Acta Biochim. Pol. 58, 397–404 (2011).
Grossi, G. et al. Late cellular effects of 12C ions. Nuovo Cimento C 31, 39–47 (2008).
Zahnreich, S. et al. Radiation-induced premature senescence is associated with specific cytogenetic changes. Mutat. Res. 701, 60–66 (2010).
Vavrova, J. & Rezacova, M. The importance of senescence in ionizing radiation-induced tumour suppression. Folia Biol. 57, 41–46 (2011).
Shah, D. J., Sachs, R. K. & Wilson, D. J. Radiation-induced cancer: a modern view. Br. J. Radiol. 85, 1166–1173 (2012).
Yentrapalli, R. et al. The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation. PLoS ONE 8, e70024 (2013).
Favero, G., Paganelli, C., Buffoli, B., Rodella, L. F. & Rezzani, R. Endothelium and its alterations in cardiovascular diseases: life style intervention. Biomed. Res. Int. 2014, 801896 (2014).
Wang, Y., Boerma, M. & Zhou, D. Ionizing radiation-induced endothelial cell senescence and cardiovascular diseases. Radiat. Res. 186, 135–161 (2016).
Lowe, D. & Raj, K. Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression. Aging Cell. 13, 900–910 (2014).
Yarnold, J. & Vozenin Brotons, M.-C. Pathogenetic mechanisms in radiation fibrosis. Radiother. Oncol. 97, 149–161 (2010).
Libby, P. Inflammation in atherosclerosis: transition from theory to practice. Circ. J. 420, 866–884 (2002).
Hansson, G. K., Libby, P. & Tabas, I. Inflammation and plaque vulnerability. J. Intern. Med. 278, 483–493 (2015).
Lehmann, H. I. et al. Feasibility study on cardiac arrhythmia ablation using high-energy heavy ion beams. Sci. Rep. 6, 38895 (2016).
Lavi, S., Gaitini, D., Milloul, V. & Jacob, G. Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction. Am. J. Physiol. Heart Circ. Physiol. 291, H1856–H1861 (2006).
Wilkerson, M. K. et al. Simulated microgravity enhances cerebral artery vasoconstriction and vascular resistance through endothelial nitric oxide mechanism. Am. J. Physiol. Heart Circ. Physiol. 288, H1652–H1661 (2005).
LaRocca, T. J., Martens, C. R. & Seals, D. R. Nutrition and other lifestyle influences on arterial aging. Ageing Res. Rev. 39, 106–119 (2017).
Lakatta, E. G. & Levy, D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation 107, 139–146 (2003).
Hall, S. et al. Protection against radiotherapy-induced toxicity. Antioxid. 5, 22 (2016).
Healy, G. N. et al. Breaks in sedentary time: beneficial associations with metabolic risk. Diabetes Care. 31, 661–666 (2008).
Lane, H. W., Bourland, C., Barrett, A., Heer, M. & Smith, S. M. The role of nutritional research in the success of human space flight. Adv. Nutr. 4, 521–523 (2013).
Zabel, P., Bamsey, M., Schubert, D. & Tajmar, M. Review and analysis of over 40 years of space plant growth systems. Life Sci. Space Res. 10, 1–16 (2016).
Boehm, F., Edge, R., Truscott, T. G. & Witt, C. A dramatic effect of oxygen on protection of human cells against γ-radiation by lycopene. FEBS Lett. 590, 1086–1093 (2016).
Martens, C. R. & Seals, D. R. Practical alternatives to chronic caloric restriction for optimizing vascular function with ageing. J. Physiol. 594, 7177–7195 (2016).
Pietrofesa, R. et al. Novel double-hit model of radiation and hyperoxia-induced oxidative cell damage relevant to space travel. Int. J. Mol. Sci. 17, 953 (2016).
NASA Exploration Atmospheres Working Group. Recommendations for exploration spacecraft internal atmospheres: the final report of the NASA exploration atmospheres working group (National Aeronautics and Space Administration, 2010).
Tinganelli, W. et al. Kill-painting of hypoxic tumours in charged particle therapy. Sci. Rep. 5, 17016 (2015).
Durante, M. Space radiation protection: destination Mars. Life Sci. Space Res. 1, 2–9 (2014).
Slaba, T. C. et al. Optimal shielding thickness for galactic cosmic ray environments. Life Sci. Space Res. 12, 1–15 (2017).
Work in the R.L.H. laboratory is supported by the Canadian Space Agency Contracts 9F007-020213/001/ST, 9F007-046025/001/ST, 9F007-052819/001/ST, 9F053-111259, and 9F053-120610. Work on space radiation protection by M.D. has been supported by the European Space Agency (ESA) under grants IBER and ROSSINI. Work on radiation-induced cardiovascular disease has been supported by the Euratom 7th FP under grant agreement no. 295823 (PROCARDIO). The authors thank Emanuele Scifoni (TIFPA-INFN, Trento, Italy) for his assistance with Figures.
The authors declare no competing financial interests.
Grays are units of absorbed radiation dose; 1 Gy = 1 J/kg.
Sieverts are derived units of ionizing radiation dose and are a measure of the health effect of low levels of ionizing radiation on the human body.
- HZE particles
High-energy and high-charge particles; they are conventionally identified as the ions heavier than helium that can cross a shield of 5 g/cm2 of aluminium.
- Van Allen belts
Giant swathes of magnetically trapped, highly energetic charged particles originating from solar wind and galactic cosmic rays that surround the Earth at an altitude of 500–58,000 km.
- Solar particle events
Strong emissions of charged particles from the Sun that are associated with solar flares or coronal mass ejections.
- High-energy protons
Protons in galactic cosmic rays peak around 1 GeV, whereas those trapped in the Van Allen belts have energy in the range 10–500 MeV.
- Fission-spectrum neutrons
Neutrons produced in nuclear reactors; typically the energy peaks around 1 MeV and has a tail reaching 5–6 MeV.
- Fast neutrons
High-energy neutrons that are produced by the interaction of high-energy protons with shielding materials.
- Linear energy transfer
Charged particle energy loss per unit track length; in radioprotection, linear energy transfer is generally expressed in keV/μm in water.
- Relative biological effectiveness
The ratio of the reference radiation dose and the test radiation dose producing the same effect
- Dietary Approaches to Stop Hypertension diet
An eating plan that encourages reduction in sodium intake with increases in foods rich in potassium, calcium, and magnesium.
- Nuclear fragmentation
The fragmentation of the projectile and/or target nuclei as a result of nuclear interactions between energetic heavy ions and target atoms.
About this article
Cite this article
Hughson, R., Helm, A. & Durante, M. Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat Rev Cardiol 15, 167–180 (2018). https://doi.org/10.1038/nrcardio.2017.157
Simulated weightlessness induces cognitive changes in rats illustrated by performance in operant conditioning tasks
Life Sciences in Space Research (2021)
Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects
Experimental Biology and Medicine (2021)
Frontiers in Cardiovascular Medicine (2021)
Radiation and Environmental Biophysics (2021)