ArticleThe American journal of pathology2002
Deficiency of microvascular thrombomodulin and up-regulation of protease-activated receptor-1 in irradiated rat intestine: possible link between endothelial dysfunction and chronic radiation fibrosis.
Article in The American journal of pathology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 148 citations in OpenAlex.
- Radiomitigators: Breakthroughs in Post-Radiation Recovery.Antioxidants (Basel, Switzerland) · 2026Review
- Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects.Antioxidants (Basel, Switzerland) · 2023Review
- Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis.International journal of molecular sciences · 2022Review
- Radiotherapy-Specific Chronic Pain Syndromes in the Cancer Population: An Evidence-Based Narrative Review.Advances in therapy · 2021Review
- Polysaccharides extracted from Rheum tanguticum ameliorate radiation-induced enteritis via activation of Nrf2/HO-1.Journal of radiation research · 2021Article
- The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil.Frontiers in oncology · 2021Review
- Neoadjuvant Radiotherapy-Related Wound Morbidity in Soft Tissue Sarcoma: Perspectives for Radioprotective Agents.Cancers · 2020Review
- Fractionated radiation suppresses Kruppel-like factor 2 pathway to a greater extent than by single exposure to the same total dose.Scientific reports · 2020Article
- A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress.Molecules (Basel, Switzerland) · 2019Review
- HMGB1-modified mesenchymal stem cells attenuate radiation-induced vascular injury possibly via their high motility and facilitation of endothelial differentiation.Stem cell research & therapy · 2019Article
- Pathological effects of ionizing radiation: endothelial activation and dysfunction.Cellular and molecular life sciences : CMLS · 2019Review
- A Rat Model of Radiation Vasculitis for the Study of Mesenchymal Stem Cell-Based Therapy.BioMed research international · 2019Article
- Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2019Article
- Utilization of Vitamin E Analogs to Protect Normal Tissues While Enhancing Antitumor Effects.Seminars in radiation oncology · 2019Review
- Radiation, inflammation and the immune response in cancer.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- The importance of the vascular endothelial barrier in the immune-inflammatory response induced by radiotherapy.The British journal of radiology · 2018Review
- Fibrinogen deficiency suppresses the development of early and delayed radiation enteropathy.World journal of gastroenterology · 2017Article
- Fractionated abdominal irradiation induces intestinal microvascular changes in an in vivo model of radiotherapy-induced gut toxicity.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2017Article
- Cardiovascular diseases related to ionizing radiation: The risk of low-dose exposure (Review).International journal of molecular medicine · 2016Review
- Pathology and biology of radiation-induced cardiac disease.Journal of radiation research · 2016Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Microvascular injury is believed to be mechanistically involved in radiation fibrosis, but direct molecular links between endothelial dysfunction and radiation fibrosis have not been established in vivo. We examined radiation-induced changes in endothelial thrombomodulin (TM) and protease-activated receptor-1 (PAR-1) in irradiated intestine, and their relationship to structural, cellular, and molecular aspects of radiation injury. Rat small intestine was locally exposed to fractionated X-radiation. Structural injury was assessed 24 hours and 2, 6, and 26 weeks after the last radiation fraction using quantitative histology and morphometry. TM, neutrophils, transforming growth factor-beta, and collagens I and III were assessed by quantitative immunohistochemistry. PAR-1 protein was localized immunohistochemically, and cells expressing TM or PAR-1 transcript were identified by in situ hybridization. Steady-state PAR-1 mRNA levels in intestinal smooth muscle were determined using laser capture microdissection and competitive reverse transcriptase-polymerase chain reaction. Radiation caused a sustained, dose-dependent decrease in microvascular TM. The number of TM-positive vessels correlated with all parameters of radiation enteropathy and, after adjusting for radiation dose and observation time in a statistical model, remained independently associated with neutrophil infiltration, intestinal wall thickening, and collagen I accumulation. PAR-1 immunoreactivity and transcript increased in vascular and intestinal smooth muscle cells in irradiated intestine. PAR-1 mRNA increased twofold in irradiated intestinal smooth muscle. Intestinal irradiation up-regulates PAR-1 and causes a dose-dependent, sustained deficiency of microvascular TM that is independently associated with the severity of radiation toxicity. Interventions aimed at preserving or restoring endothelial TM or blocking PAR-1 should be explored as strategies to increase the therapeutic ratio in clinical radiation therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.