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Publications

Journal Article Epublish

PubMed: 41752137 DOI: 10.3390/ijms27042001

Pre-Exposure Prophylaxis with Vasculotide Enhances Survival and Alleviates Hematopoietic and Gastrointestinal Injury Following Lethal Total Body Irradiation.

Int J Mol Sci 27(4)

Authors: Li Wang, Bin Lin, Min Zhai, Lisa Hull, Asher Rothstein, Katherine S Cleveland, Hengying Ellery, Wanchang Cui, Mang Xiao, Juliann G Kiang

Affiliations

  • Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Bethesda, MD 20817, USA. Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Bethesda, MD 20817, USA.
  • Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. Bethesda, MD 20817, USA.
  • Comparative Pathology, Department of Laboratory Animal Resources, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
  • Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Abstract

No US Food and Drug Administration (FDA)-approved prophylaxis is currently available for Acute Radiation Syndrome (ARS), which remains a significant threat to military and civilian populations. In this study, we investigated Vasculotide (VT), a Tie2 receptor agonist mimic, as a novel pre-exposure prophylaxis designed to stabilize the vascular endothelium, one of primary targets of radiation-induced damage. To evaluate its efficacy, female B6D2F1/J mice were exposed to 9.5 Gy total body irradiation (TBI), with VT administered subcutaneously at 12 and 2 h prior to exposure. Assessments included 30-day survival, biomarkers of vascular injury, proinflammatory cytokine/chemokine profiling, and evaluation of hematopoietic (H) and gastrointestinal (GI) recovery. Our findings demonstrate that VT significantly increased 30-day survival in a dose-dependent manner, achieving a 30% survival advantage at the 20 μg/kg dose. Furthermore, VT provided robust protection against radiation-induced vascular activation and injury, effectively alleviating damage to the bone marrow (BM) and GI tract. Taken together, these results identify VT as a promising prophylactic countermeasure for ARS. By targeting the Tie2 pathway to preserve vascular integrity, VT addresses a critical gap in medical countermeasures, offering a viable strategy to enhance survival and accelerate multi-organ recovery in radiological mass-casualty scenarios.

MeSH

Endothelium, Vascular, Pre-Exposure Prophylaxis, Whole-Body Irradiation, Recycling, Acute Radiation Syndrome