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.

Astronauts in space vehicles beyond low-Earth orbit will be exposed to high charge and energy (HZE) ions, and there is concern about potential adverse effects on the cardiovascular system. Thus far, most animal studies that assess cardiac effects of HZE particles have included only males. This study assessed the effects of oxygen ions (¹⁶O) as a representative ion of the intravehicular radiation environment on the heart of female mice.

Female C57BL/6 J mice at 6 months of age were exposed to ¹⁶O (600 MeV/n) at 0.25-0.26 Gy/min to a total dose of 0, 0.1, or 0.25 Gy. Cardiac function and abdominal aorta blood velocity were measured with ultrasonography at 3, 5, 7, and 9 months after irradiation. At 2 weeks, 3 months, and 9 months, cardiac tissue was collected to assess collagen deposition and markers of immune cells.

Ultrasonography revealed increased left ventricle mass, diastolic volume and diameter but there was no change in the abdominal aorta. There was no indication of cardiac fibrosis however, a 75 kDa peptide of left ventricular collagen type III and α-smooth muscle cell actin were increased suggesting some remodeling had occurred. Left ventricular protein levels of the T-cell marker CD2 was significantly increased at all time points, while the neutrophil marker myeloperoxidase was decreased at 2 weeks and 9 months.

These results taken together suggest ¹⁶O ion exposure did not result in cardiac fibrosis or cardiac dysfunction in female mice. However, it does appear mild cardiac remodeling occurs in response to HZE radiation.

There is an ongoing shift in demographics such that older persons will outnumber young persons in the coming years, and with it age-associated tissue attrition and increased diseases and disorders. There has been increased information on the association of the aging process with dysregulation of hematopoietic stem (HSC) and progenitor (HPC) cells, and hematopoiesis. This review provides an extensive up-to date summary on the literature of aged hematopoiesis and HSCs placed in context of potential artifacts of the collection and processing procedure, that may not be totally representative of the status of HSCs in their in vivo bone marrow microenvironment, and what the implications of this are for understanding aged hematopoiesis. This review covers a number of interactive areas, many of which have not been adequately explored. There are still many unknowns and mechanistic insights to be elucidated to better understand effects of aging on the hematopoietic system, efforts that will take multidisciplinary approaches, and that could lead to means to ameliorate at least some of the dysregulation of HSCs and HPCs associated with the aging process. Graphical Abstract.

A manned mission to Mars has been contemplated by the world's largest space agencies for a number of years. The duration of the trip would necessitate a much longer exposure to deep space radiation than any human has ever been exposed to in the past. Concern regarding cancer risk has thus far stalled the progress of deep space exploration; however, the effect of space radiation on the cardiovascular system is significantly less well understood.

Damage by radiation in space is mediated by a number of sources, including X-rays, protons and heavier charged atomic nuclei (HZE ions, the high-energy component of galactic cosmic rays). Previously, only lunar mission astronauts have been exposed to significant deep space radiation, with all other missions being low earth orbits only. The effect of this radiation on the human body has been inconclusively studied, and the long-term damage caused to the vascular endothelium by this radiation due to the effect of high-energy particles is not well known.

Current radiation shielding technology, which would be viable for use in spacecraft, would not eliminate radiation risk. Similar to how a variety of shielding techniques are used every day by radiographers, again without full risk elimination, we need to explore and better understand the effect of deep space radiation in order to ensure the safety of those on future space missions.

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.

This article provides an overview of studies addressing effects of ionizing radiation on the heart. Clinical studies have identified early and late manifestations of radiation-induced heart disease, a side effect of radiation therapy to tumors in the chest when all or part of the heart is situated in the radiation field. Studies in preclinical animal models have contributed to our understanding of the mechanisms by which radiation may injure the heart. More recent observations in human subjects suggest that ionizing radiation may have cardiovascular effects at lower doses than was previously thought. This has led to examinations of low-dose photons and low-dose charged particle irradiation in animal models. Lastly, studies have started to identify non-invasive methods for detection of cardiac radiation injury and interventions that may prevent or mitigate these adverse effects. Altogether, this ongoing research should increase our knowledge of biological mechanisms of cardiovascular radiation injury, identify non-invasive biomarkers for early detection, and potential interventions that may prevent or mitigate these adverse effects.

DNA methylation is a key epigenetic mechanism, needed for proper control over the expression of genetic information and silencing of repetitive elements. Exposure to ionizing radiation, aside from its strong genotoxic potential, may also affect the methylation of DNA, within the repetitive elements, in particular. In this study, we exposed C57BL/6J male mice to low absorbed mean doses of two types of space radiation-proton (0.1 Gy, 150 MeV, dose rate 0.53 ± 0.08 Gy/min), and heavy iron ions ((56)Fe) (0.5 Gy, 600 MeV/n, dose rate 0.38 ± 0.06 Gy/min). Radiation-induced changes in cardiac DNA methylation associated with repetitive elements were detected. Specifically, modest hypomethylation of retrotransposon LINE-1 was observed at day 7 after irradiation with either protons or (56)Fe. This was followed by LINE-1, and other retrotransposons, ERV2 and SINE B1, as well as major satellite DNA hypermethylation at day 90 after irradiation with (56)Fe. These changes in DNA methylation were accompanied by alterations in the expression of DNA methylation machinery and affected the one-carbon metabolism pathway. Furthermore, loss of transposable elements expression was detected in the cardiac tissue at the 90-day time-point, paralleled by substantial accumulation of mRNA transcripts, associated with major satellites. Given that the one-carbon metabolism pathway can be modulated by dietary modifications, these findings suggest a potential strategy for the mitigation and, possibly, prevention of the negative effects exerted by ionizing radiation on the cardiovascular system. Additionally, we show that the methylation status and expression of repetitive elements may serve as early biomarkers of exposure to space radiation.

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.

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.

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.

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.