Countermeasures for cardiac fibrosis in space travel: It takes more than a towel for a hitchhiker's guide to the galaxy

Author:

Beheshti Afshin1ORCID,Paar Vera2,Jiang Siyi3ORCID,Enriquez Angela3,Kim JangKeun4,Brunetta Henver5,Muratani Masafumi6ORCID,Kubik Angela7,Allen Noah7ORCID,Blaber Elizabeth8ORCID,Overbey Eliah4,Altinok Selin9ORCID,Sanchez-Hodge Rebecca10,Oswalt Leah10ORCID,Kaufman Brett11ORCID,Mori Marcelo12ORCID,Motloch Lukas13,Mason Christopher4ORCID,Schisler Jonathan14ORCID,Jirak Peter15

Affiliation:

1. NASA Ames Research Center

2. Universtiy Clinic Salzburg

3. Division of Cardiology, Center for Metabolism and Mitochondrial Medicine and Vascular Medicine Institute, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States

4. Weill Cornell Medicine

5. University of Guelph

6. University of Tsukuba

7. Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA

8. Rensselaer Polytechnic Institute

9. Department of Neurosurgery, Yale School of Medicine, New Haven, CT, 06510

10. McAllister Heart Institute and Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

11. University of Pennsylvania School of Veterinary Medicine

12. Institute of Biology, University of Campinas (Unicamp)

13. Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University, Salzburg, Austria

14. The University of North Carolina at Chapel Hill, Chapel Hill

15. Paracelsus Medical University of Salzburg

Abstract

Abstract MicroRNAs (miRNAs) are small, non-coding RNA molecules that are post-transcriptional regulators of gene expression. miRNAs have been shown to be key regulators of complicated pathological processes and hence great biomarkers for the early prediction of diseases, such as cardiovascular diseases and radiation-associated alteration after spaceflight. In this study, we present possible antagomir treatments targeting three different miRNAs, miR-16-5p, miR-125b-5p, and let-7a-5p, to mitigate the activity of the spaceflight environment in cardiovascular diseases. We focus on three proteins of interest associated with fibrotic remodeling, TGF-β1, SMAD3, and COL1, analyzing the molecular outcomes of antagomir treatment when exposed to Galactic Cosmic Radiation (GCR), Solar Particle Events (SPE) radiation, and microgravity. These proteins have been shown to play different fibrotic and antifibrotic roles and show molecular changes associated with exposure to the space environment. Furthermore, our results demonstrate the therapeutic potential of antagomirs as a countermeasure for future spaceflight missions.

Publisher

Research Square Platform LLC

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