NYMC Faculty Publications

Lifetime Evaluation of Left Ventricular Structure and Function in Male C57BL/6J Mice After Gamma and Space-Type Radiation Exposure

Authors

Agnieszka Brojakowska, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cedric J. Jackson, National Institute of Aerospace, Hampton, VA 23666, USA.
Malik Bisserier, Department of Cell Biology and Anatomy and Physiology, New York Medical College, Valhalla, NY 10595, USA.
Mary K. Khlgatian, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Cynthia Grano, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Steve R. Blattnig, National Aeronautics and Space Administration, Hampton, VA 23669, USA.
Shihong Zhang, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kenneth M. Fish, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vadim Chepurko, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Elena Chepurko, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Virginia Gillespie, Center for Comparative Medicine and Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ying Dai, Center for Comparative Medicine and Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Brooke Lee, Department of Emergency Medicine, Dorothy M. Davis Heart Lung and Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Venkata Naga Garikipati, Department of Emergency Medicine, Dorothy M. Davis Heart Lung and Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Lahouaria Hadri, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Raj Kishore, Department of Cardiovascular Sciences, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
David A. Goukassian, Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Author Type(s)

Faculty

DOI

10.3390/ijms24065451

Journal Title

International Journal of Molecular Sciences

Document Type

Article

Publication Date

3-13-2023

Department

Cell Biology and Anatomy

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 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.

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