Lifetime evaluation of left ventricular structure and function in male ApoE null mice after gamma and space-type radiation exposure
Year: 2023
Type: article
Abstract: The space radiation (IR) environment contains high charge and energy (HZE) nuclei emitted from galactic cosmic rays with the ability to overcome current shielding strategies, posing increased IR-induced cardiovascular disease risks for astronauts on prolonged space missions. Little is known about the effect of 5-ion simplified galactic cosmic ray simulation (simGCRsim) exposure on left ventricular (LV) function. Three-month-old, age-matched male Apolipoprotein E (ApoE) null mice were irradiated with 137Cs gamma (γ; 100, 200, and 400 cGy) and simGCRsim (50, 100, 150 cGy all at 500 MeV/nucleon (n)). LV function was assessed using transthoracic echocardiography at early/acute (14 and 28 days) and late/degenerative (365, 440, and 660 days) times post-irradiation. As early as 14 and 28-days post IR, LV systolic function was reduced in both IR groups across all doses. At 14 days post-IR, 150 cGy simGCRsim-IR mice had decreased diastolic wall strain (DWS), suggesting increased myocardial stiffness. This was also observed later in 100 cGy γ-IR mice at 28 days. At later stages, a significant decrease in LV systolic function was observed in the 400 cGy γ-IR mice. Otherwise, there was no difference in the LV systolic function or structure at the remaining time points across the IR groups. We evaluated the expression of genes involved in hemodynamic stress, cardiac remodeling, inflammation, and calcium handling in LVs harvested 28 days post-IR. At 28 days post-IR, there is increased expression of Bnp and Ncx in both IR groups at the lowest doses, suggesting impaired function contributes to hemodynamic stress and altered calcium handling. The expression of Gals3 and β-Mhc were increased in simGCRsim and γ-IR mice respectively, suggesting there may be IR-specific cardiac remodeling. IR groups were modeled to calculate the Relative Biological Effectiveness (RBE) and Radiation Effects Ratio (RER). No lower threshold was determined using the observed dose-response curves. These findings do not exclude the possibility of the existence of a lower IR threshold or the presence of IR-induced cardiovascular disease (CVD) when combined with additional space travel stressors, e.g., microgravity.
Source: Frontiers in Physiology
Authors: Agnieszka Brojakowska, Cedric J. Jackson, Malik Bisserier, Mary K. Khlgatian, Vineeta Jagana, Abrisham Eskandari, Cynthia Grano, Steve R. Blattnig, Shihong Zhang, Kenneth M. Fish, Vadim Chepurko, Elena Chepurko, Virginia Gillespie, Ying Dai, Amit Kumar Rai, Venkata Naga Srikanth Garikipati, Lahouaria Hadri, Raj Kishore, David A. Goukassian
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,295
Funders: National Aeronautics and Space Administration, Cardiovascular Medical Research and Education Fund, National Synchrotron Radiation Laboratory, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, Brookhaven National Laboratory
Awards: WE ANTICIPATE THAT THE RESULTS OF OUR PROPOSED WORK MAY BE BENEFICIAL FOR HUMAN SPACE EXPLORATION AND COULD (1) DETERMINE SINGLE LOW-DOSE 1H 56FE AND MIXED FIELD DOSE-RESPONSES RADIO-BIOLOGICALLY EFFECTIVE IR THRESHOLDS IN THE HEART AND CARDIAC VASCULATURE AND WHETHER GENDER DIFFERENCES COULD MODIFY RADIO-BIOLOGICALLY EFFECTIVE IR THRESHOLDS FOR CV RISK ESTIMATES; 2) DETERMINE WHETHER SPACE RADIATION LEADS TO MODIFICATIONS IN THE CIRCULATING EXOSOMAL CARGO CONTENTS AND WHETHER IR-INDUCED EXOSOMAL CARGO MODULATIONS ARE REFLECTIVE OF SUBCLINICAL CHANGES IN THE CELLS AND ORGANS OF ORIGIN; 3) ASCERTAIN IF MODULATIONS OF EXOSOMAL CARGO MAY BE REPRESENTATIVE OF CHRONIC OXIDATIVE STRESS AND INFLAMMATION AND COULD SERVE AS EARLY BIOMARKERS OF IR-INDUCED CV DISEASE INITIATION AND PROGRESSION; 4) INTEGRATE PHYSIOLOGICAL CV ENDPOINT DATA SETS WITH GENE EXPRESSION AND EPIGENETIC DATA TO IDENTIFY BIO-MARKERS IN BIO-FLUIDS THAT COULD BE USED FOR PREDICTION OF ASYMPTOMATIC CV DISEASE IN THE SETTING OF SPACE IR WHICH WILL INCLUDE KNOWN EARLY AND INTERMEDIATE BIO-MARKERS OF CARDIAC DAMAGE INFLAMMATION AND OXIDATIVE STRESS AS WELL AS CURRENTLY UNKNOWN NOVEL RADIATION-ASSOCIATED CARDIAC BIO-MARKERS., G4013209848, Role of SIN3a in the epigenetic regulation of the Bone Morphogenetic Protein Receptor Type 2 in pulmonary arterial hypertension, FACILITATE ESTABLISHMENT AND OPERATION OF SCIENCE AND RESEARCH INSTITUTE, ARID1a and Chromatin Landscape in Pulmonary Vascular Disease, Role of Epigenetic Regulator SIN3a in Pulmonary Endothelial Cells, Role of Epac1 in the Pathogenesis of Pulmonary Fibrosis, Health AI and Data Science in Cardiovascular and Pulmonary Disease: Application and Bioethics (HARP-BIO), The Chromatin Remodeling Factor ARID1a and the Epigenetic Landscape In Pulmonary Arterial Hypertension
OpenAlex ID: W4388973216