ArticleBlood2022
Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude.
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45 citing papers in PubMed, 67 citations in OpenAlex.
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Authors and funding
20 authors at 5 institutions in 3 countries.
Meiquan LiKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Xiaopeng TangKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Zhiyi LiaoKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Chuanbin ShenDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-4635-5160
Ruomei ChengKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Mingqian FangKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Gan WangKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.ORCID 0000-0002-6266-8503
Ya LiDepartment of Clinical Laboratory, Yunnan Key Laboratory of Laboratory Medicine, Yunnan Innovation Team of Clinical Laboratory and Diagnosis, the First Affiliated Hospital of Kunming Medical University, Kunming, China.
Shuzhen TangDepartment of Clinical Laboratory, the People's Hospital of Diqing Tibetan Autonomous Prefecture, Shangri-La, China.
Li XieDepartment of Clinical Laboratory, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
Zhiye ZhangKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.ORCID 0000-0002-1661-2277
Peter Muiruri KamauKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
James MwangiKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Qiumin LuKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Yaxiong LiDepartment of Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, China.
Yuming WangDepartment of Clinical Laboratory, the Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Daniel Thomas MacKeiganDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, ON, Canada.
Eric G CerenziaDepartment of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael's Hospital and Toronto Platelet Immunobiology Group, Toronto, ON, Canada.
Heyu NiDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Ren LaiKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology-The Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming, China.
Chinese University of Hong Kong · HKSt. Michael's Hospital · CAKunming Medical University · CNGuangxi Medical University · CNKunming University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies have shown significantly increased thromboembolic events at high altitude. We recently reported that transferrin could potentiate blood coagulation, but the underlying mechanism for high altitude-related thromboembolism is still poorly understood. Here, we examined the activity and concentration of plasma coagulation factors and transferrin in plasma collected from long-term human residents and short-stay mice exposed to varying altitudes. We found that the activities of thrombin and factor XIIa (FXIIa) along with the concentrations of transferrin were significantly increased in the plasma of humans and mice at high altitudes. Furthermore, both hypoxia (6% O2) and low temperature (0°C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1α (HIF-1α) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1α binding site, and consequently, to induce hypercoagulability by potentiating thrombin and FXIIa. Importantly, thromboembolic disorders and pathological insults in mouse models induced by both hypoxia and low temperature were ameliorated by transferrin interferences, including transferrin antibody treatment, transferrin downregulation, and the administration of our designed peptides that inhibit the potentiation of transferrin on thrombin and FXIIa. Thus, low temperature and hypoxia upregulated transferrin expression-promoted hypercoagulability. Our data suggest that targeting the transferrin-coagulation pathway is a novel and potentially powerful strategy against thromboembolic events caused by harmful environmental factors under high-altitude conditions.
Indexed as
AltitudeThrombophiliaAnimalsHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitMiceTemperatureThrombinTransferrinHypoxia-Inducible Factor 1, alpha SubunitThrombinTransferrin
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