Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
National Institute of Aerospace, Hampton, VA 23666, USA.
Int J Mol Sci. 2023 Mar 13;24(6):5451. doi: 10.3390/ijms24065451.
The lifetime effects of space irradiation (IR) on left ventricular (LV) function are unknown. The cardiac effects induced by space-type IR, specifically 5-ion simplified galactic cosmic ray simulation (simGCRsim), are yet to be discovered. Three-month-old, age-matched, male C57BL/6J mice were irradiated with Cs gamma (γ; 100, 200 cGy) and simGCRsim (50 and 100 cGy). LV function was assessed via transthoracic echocardiography at 14 and 28 days (early), and at 365, 440, and 660 (late) days post IR. We measured the endothelial function marker brain natriuretic peptide in plasma at three late timepoints. We assessed the mRNA expression of the genes involved in cardiac remodeling, fibrosis, inflammation, and calcium handling in LVs harvested at 660 days post IR. All IR groups had impaired global LV systolic function at 14, 28, and 365 days. At 660 days, 50 cGy simGCRsim-IR mice exhibited preserved LV systolic function with altered LV size and mass. At this timepoint, the simGCRsim-IR mice had elevated levels of cardiac fibrosis, inflammation, and hypertrophy markers , , , and , suggesting that space-type IR may induce the cardiac remodeling processes that are commonly associated with diastolic dysfunction. IR groups showing statistical significance were modeled to calculate the Relative Biological Effectiveness (RBE) and Radiation Effects Ratio (RER). The observed dose-response shape did not indicate a lower threshold at these IR doses. A single full-body IR at doses of 100-200 cGy for γ-IR, and 50-100 cGy for simGCRsim-IR decreases the global LV systolic function in WT mice as early as 14 and 28 days after exposure, and at 660 days post IR. Interestingly, there is an intermediate time point (365 days) where the impairment in LV function is observed. These findings do not exclude the possibility of increased acute or degenerative cardiovascular disease risks at lower doses of space-type IR, and/or when combined with other space travel-associated stressors such as microgravity.
太空辐射（IR）对左心室（LV）功能的终生影响尚不清楚。尚未发现太空型 IR 引起的心脏效应，特别是 5 离子简化银河宇宙射线模拟（simGCRsim）。3 个月大、年龄匹配的雄性 C57BL/6J 小鼠接受 Csγ（γ；100、200 cGy）和 simGCRsim（50 和 100 cGy）照射。通过经胸超声心动图在照射后 14 天和 28 天（早期）以及 365、440 和 660 天（晚期）评估 LV 功能。我们在三个晚期时间点测量血浆中的内皮功能标志物脑钠肽。我们评估了 660 天照射后 LV 收获的心脏重构、纤维化、炎症和钙处理相关基因的 mRNA 表达。所有 IR 组在 14、28 和 365 天均出现整体 LV 收缩功能受损。在 660 天，50 cGy simGCRsim-IR 小鼠表现出 LV 收缩功能保留，但 LV 大小和质量发生改变。此时，simGCRsim-IR 小鼠的心脏纤维化、炎症和肥大标志物水平升高，表明太空型 IR 可能诱导与舒张功能障碍相关的心脏重构过程。显示统计学意义的 IR 组被建模以计算相对生物学效应（RBE）和辐射效应比（RER）。观察到的剂量反应形状表明，在这些 IR 剂量下，没有更低的阈值。全身单次照射 γ-IR 的 100-200 cGy 或 simGCRsim-IR 的 50-100 cGy，可使 WT 小鼠的整体 LV 收缩功能早在暴露后 14 和 28 天以及照射后 660 天受损。有趣的是，在 365 天观察到 LV 功能受损的中间时间点。这些发现并不排除在太空型 IR 的较低剂量下或与微重力等其他太空旅行相关应激源结合时，急性或退行性心血管疾病风险增加的可能性。
