Proton irradiation initially improved but later declined cardiac function by 10 months, whereas iron ion irradiation caused early cardiac dysfunction and worsened post-myocardial infarction recovery.
Does low-dose whole-body proton or iron ion irradiation affect cardiac function and remodeling in mice during normal aging and post-myocardial infarction?
Low-dose proton and iron ion irradiation induce distinct, time-dependent changes in cardiac function and remodeling, highlighting potential long-term cardiovascular risks for space exploration and charged particle radiotherapy.
Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1)H; 0.5 Gy, 1 GeV) and iron ion ((56)Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56)Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56)Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.
Yan et al. (Wed,) conducted a other in Normal aging and acute myocardial ischemia. Low dose ionizing particle radiation (proton and iron ion) vs. Sham-irradiated control was evaluated on Cardiac function and remodeling (echocardiography and hemodynamics). Proton irradiation initially improved but later declined cardiac function by 10 months, whereas iron ion irradiation caused early cardiac dysfunction and worsened post-myocardial infarction recovery.