Lifetime Evaluation of Left Ventricular Structure and Function in Male C57BL/6J Mice after Gamma and Space-Type Radiation Exposure
Year: 2023
Type: article
Abstract: 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 137Cs 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 Tgfβ1, Mcp1, Mmp9, and βmhc, 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.
DOI: 10.3390/ijms24065451
Authors: Agnieszka Brojakowska, Cedric J. Jackson, Malik Bisserier, Mary K. Khlgatian, Cynthia Grano, Steve R. Blattnig, Shihong Zhang, Kenneth M. Fish, Vadim Chepurko, Elena Chepurko, Virginia Gillespie, Ying Dai, Brooke Lee, Venkata Naga Srikanth Garikipati, Lahouaria Hadri, Raj Kishore, David A. Goukassian
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,780
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., Training Program in Molecular and Cellular Cardiology, G6240043616, G8034055945, ARID1a and Chromatin Landscape in Pulmonary Vascular Disease, Interactions of SERCA2a and BMPRII in Vascular Disease, Role of Epac1 in the Pathogenesis of Pulmonary Fibrosis, The Chromatin Remodeling Factor ARID1a and the Epigenetic Landscape In Pulmonary Arterial Hypertension
OpenAlex ID: W4324056860