{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:04:03Z","timestamp":1792069443047,"version":"4.4.0"},"reference-count":62,"publisher":"American Society of Hematology","issue":"19","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013related 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\u00b0C), 2 critical high-altitude factors, enhanced hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) levels to promote the expression of the transferrin gene, whose enhancer region contains HIF-1\u03b1 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\u2013promoted 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.<\/jats:p>","DOI":"10.1182\/blood.2022016410","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T11:03:07Z","timestamp":1661857387000},"page":"2063-2075","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":78,"title":["Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude"],"prefix":"10.1182","volume":"140","author":[{"given":"Meiquan","family":"Li","sequence":"first","affiliation":[{"name":"1Key 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"},{"name":"2College of Agriculture and Life Sciences, Kunming University, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Tang","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"3Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Liao","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"4Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-5160","authenticated-orcid":false,"given":"Chuanbin","family":"Shen","sequence":"additional","affiliation":[{"name":"5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada"},{"name":"6Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital and Toronto Platelet Immunobiology Group, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruomei","family":"Cheng","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"4Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqian","family":"Fang","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"4Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-8503","authenticated-orcid":false,"given":"Gan","family":"Wang","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"3Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Li","sequence":"additional","affiliation":[{"name":"7Department 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Tang","sequence":"additional","affiliation":[{"name":"8Department of Clinical Laboratory, the People\u2019s Hospital of Diqing Tibetan Autonomous Prefecture, Shangri-La, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xie","sequence":"additional","affiliation":[{"name":"9Department of Clinical Laboratory, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1661-2277","authenticated-orcid":false,"given":"Zhiye","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"3Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Muiruri","family":"Kamau","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"4Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mwangi","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"4Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiumin","family":"Lu","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"3Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxiong","family":"Li","sequence":"additional","affiliation":[{"name":"10Department of Cardiovascular Surgery, Yan\u2019an Affiliated Hospital of Kunming Medical University, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Wang","sequence":"additional","affiliation":[{"name":"11Department of Clinical Laboratory, the Second Affiliated Hospital of Kunming Medical University, Kunming, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Thomas","family":"MacKeigan","sequence":"additional","affiliation":[{"name":"6Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital and Toronto Platelet Immunobiology Group, Toronto, ON, Canada"},{"name":"12Department of Physiology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Cerenzia","sequence":"additional","affiliation":[{"name":"6Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital and Toronto Platelet Immunobiology Group, Toronto, ON, Canada"},{"name":"12Department of Physiology, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyu","family":"Ni","sequence":"additional","affiliation":[{"name":"5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada"},{"name":"6Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, St. Michael\u2019s Hospital and Toronto Platelet Immunobiology Group, Toronto, ON, Canada"},{"name":"12Department of Physiology, University of Toronto, Toronto, ON, Canada"},{"name":"13Canadian Blood Services Centre for Innovation, Toronto, ON, Canada"},{"name":"14Department of Medicine, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Lai","sequence":"additional","affiliation":[{"name":"1Key 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"},{"name":"3Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"9242","key":"2022111016254146800_bib1","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(00)03165-2","article-title":"Association between acute hypobaric hypoxia and\u00a0activation of coagulation in human\u00a0beings","volume":"356","author":"Bendz","year":"2000","journal-title":"Lancet"},{"issue":"4","key":"2022111016254146800_bib2","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1152\/japplphysiol.00110.2017","article-title":"High-altitude champions: birds that live and migrate at altitude","volume":"123","author":"Lagu\u00eb","year":"2017","journal-title":"J\u00a0Appl Physiol"},{"issue":"4","key":"2022111016254146800_bib3","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1152\/physrev.1991.71.4.1135","article-title":"Physiological adaptation to high altitude: oxygen transport in mammals and birds","volume":"71","author":"Monge","year":"1991","journal-title":"Physiol Rev"},{"issue":"12","key":"2022111016254146800_bib4","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1152\/japplphysiol.00248.2015","article-title":"Adaptation of iron requirement to hypoxic conditions at high altitude","volume":"119","author":"Gassmann","year":"2015","journal-title":"J\u00a0Appl Physiol"},{"issue":"11","key":"2022111016254146800_bib5","doi-asserted-by":"crossref","first-page":"4724","DOI":"10.1182\/blood-2006-08-040006","article-title":"Strong iron\u00a0demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle","volume":"109","author":"Robach","year":"2007","journal-title":"Blood"},{"issue":"6","key":"2022111016254146800_bib6","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1002\/hep.26581","article-title":"Adaptation of iron transport and metabolism to acute high-altitude hypoxia in mountaineers","volume":"58","author":"Goetze","year":"2013","journal-title":"Hepatology"},{"issue":"3","key":"2022111016254146800_bib7","doi-asserted-by":"crossref","first-page":"1902285","DOI":"10.1183\/13993003.02285-2019","article-title":"Iron bioavailability and cardiopulmonary function during ascent to very high altitude","volume":"56","author":"Holdsworth","year":"2020","journal-title":"Eur Respir J"},{"issue":"3","key":"2022111016254146800_bib8","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1152\/jappl.1990.68.3.1186","article-title":"Unchanged in\u00a0vivo P50 at high altitude despite decreased erythrocyte age and elevated 2,3-diphosphoglycerate","volume":"68","author":"Mairb\u00e4url","year":"1990","journal-title":"J\u00a0Appl Physiol"},{"issue":"10","key":"2022111016254146800_bib9","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1182\/blood-2010-08-299859","article-title":"Modulation of hepcidin production during hypoxia-induced erythropoiesis in humans in\u00a0vivo: data from the HIGHCARE project","volume":"117","author":"Piperno","year":"2011","journal-title":"Blood"},{"issue":"5","key":"2022111016254146800_bib10","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1113\/JP281114","article-title":"Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m","volume":"599","author":"Willie","year":"2021","journal-title":"J\u00a0Physiol"},{"issue":"19","key":"2022111016254146800_bib11","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJMra1401038","article-title":"Iron-deficiency anemia","volume":"372","author":"Camaschella","year":"2015","journal-title":"N\u00a0Engl J Med"},{"issue":"11","key":"2022111016254146800_bib12","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm.2515","article-title":"Arterial thrombosis-insidious, unpredictable and deadly","volume":"17","author":"Jackson","year":"2011","journal-title":"Nat Med"},{"issue":"3","key":"2022111016254146800_bib13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1055\/s-0029-1222603","article-title":"Coagulopathies and thrombosis: usual and unusual causes and associations, part I","volume":"35","author":"Franchini","year":"2009","journal-title":"Semin Thromb Hemost"},{"issue":"10","key":"2022111016254146800_bib14","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1182\/blood-2003-03-0850","article-title":"Control of thrombus embolization and fibronectin internalization by integrin \u03b1IIb\u03b23 engagement of the fibrinogen \u03b3 chain","volume":"102","author":"Ni","year":"2003","journal-title":"Blood"},{"issue":"1","key":"2022111016254146800_bib15","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12959-016-0100-6","article-title":"Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies","volume":"14","author":"Xu","year":"2016","journal-title":"Thromb J"},{"issue":"2","key":"2022111016254146800_bib16","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1055\/s-0032-1301413","article-title":"Exposure to high altitude: a risk factor for venous thromboembolism?","volume":"38","author":"Gupta","year":"2012","journal-title":"Semin Thromb Hemost"},{"issue":"6","key":"2022111016254146800_bib17","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1139\/H07-088","article-title":"Prohibition of artificial hypoxic environments in sports: health risks rather than ethics","volume":"32","author":"Lippi","year":"2007","journal-title":"Appl Physiol Nutr Metab"},{"issue":"19","key":"2022111016254146800_bib18","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1001\/jama.295.19.2251","article-title":"Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation","volume":"295","author":"Toff","year":"2006","journal-title":"JAMA"},{"issue":"4","key":"2022111016254146800_bib19","first-page":"197","article-title":"Thrombosis as a complication of extended stay at high altitude","volume":"14","author":"Anand","year":"2001","journal-title":"Natl Med J India"},{"issue":"1","key":"2022111016254146800_bib20","first-page":"71","article-title":"Pulmonary embolism at high altitude and hyperhomocysteinemia","volume":"16","author":"Ashraf","year":"2006","journal-title":"J\u00a0Coll Physicians Surg Pak"},{"issue":"4","key":"2022111016254146800_bib21","first-page":"172","article-title":"Portal system thrombosis: a new dimension of high altitude illnesses","volume":"21","author":"Anand","year":"2000","journal-title":"Trop Gastroenterol"},{"issue":"4","key":"2022111016254146800_bib22","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.neurol.2016.11.004","article-title":"Cerebral venous thrombosis at high altitude: a systematic review","volume":"173","author":"Zavanone","year":"2017","journal-title":"Rev Neurol"},{"issue":"9","key":"2022111016254146800_bib23","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1136\/emj.2004.014613","article-title":"An unusual swelling in\u00a0the neck","volume":"22","author":"Abbasi","year":"2005","journal-title":"Emerg Med J"},{"issue":"4","key":"2022111016254146800_bib24","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1089\/ham.2016.0008","article-title":"Pulmonary embolism masquerading as high altitude pulmonary edema at high altitude","volume":"17","author":"Pandey","year":"2016","journal-title":"High Alt Med Biol"},{"issue":"4","key":"2022111016254146800_bib25","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1089\/ham.2020.0053","article-title":"Prevalence and clinical characteristics of post-thrombotic syndrome in high-altitude\u2013induced deep vein thrombosis: experience of a single tertiary care center from real-world settings","volume":"21","author":"Yanamandra","year":"2020","journal-title":"High Alt Med Biol"},{"issue":"1","key":"2022111016254146800_bib26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1089\/152702902753639513","article-title":"Stroke at high altitude: indian experience","volume":"3","author":"Jha","year":"2002","journal-title":"High Alt Med Biol"},{"issue":"2","key":"2022111016254146800_bib27","first-page":"84","article-title":"High altitude induced deep venous thrombosis: a study of 28 cases","volume":"68","author":"Shishir","year":"2006","journal-title":"Indian J Surg"},{"issue":"2","key":"2022111016254146800_bib28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.7205\/MILMED-D-10-00144","article-title":"Quantification of\u00a0the 5-year incidence of thromboembolic events in US Air Force Academy cadets in\u00a0comparison to the US Naval and Military\u00a0Academies","volume":"176","author":"Smallman","year":"2011","journal-title":"Mil Med"},{"issue":"2","key":"2022111016254146800_bib29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41422-019-0260-6","article-title":"Transferrin plays a central role in coagulation balance by interacting with clotting factors","volume":"30","author":"Tang","year":"2020","journal-title":"Cell Res"},{"issue":"5","key":"2022111016254146800_bib30","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1161\/CIRCRESAHA.119.316453","article-title":"Iron-deficiency and estrogen are associated with ischemic stroke by up-regulating transferrin to induce hypercoagulability","volume":"127","author":"Tang","year":"2020","journal-title":"Circ Res"},{"issue":"2","key":"2022111016254146800_bib31","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/jnc.15291","article-title":"Cyclooxygenase inhibition attenuates brain angiogenesis and independently decreases mouse survival under hypoxia","volume":"158","author":"Seeger","year":"2021","journal-title":"J\u00a0Neurochem"},{"issue":"13","key":"2022111016254146800_bib32","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1182\/blood-2016-07-729400","article-title":"The integrin PSI domain has an endogenous thiol isomerase function and is a novel target for antiplatelet therapy","volume":"129","author":"Zhu","year":"2017","journal-title":"Blood"},{"issue":"1","key":"2022111016254146800_bib33","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1038\/s41467-018-05806-0","article-title":"Apolipoprotein A-IV binds \u03b1IIb\u03b23 integrin and inhibits thrombosis","volume":"9","author":"Xu","year":"2018","journal-title":"Nat Commun"},{"issue":"10","key":"2022111016254146800_bib34","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1172\/JCI74630","article-title":"Plasma fibronectin supports hemostasis and regulates thrombosis","volume":"124","author":"Wang","year":"2014","journal-title":"J\u00a0Clin Invest"},{"issue":"2","key":"2022111016254146800_bib35","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s12264-019-00411-7","article-title":"Hes1 knockdown exacerbates ischemic stroke following tMCAO by increasing ER stress-dependent apoptosis via the PERK\/eIF2alpha\/ATF4\/CHOP signaling pathway","volume":"36","author":"Li","year":"2020","journal-title":"Neurosci Bull"},{"issue":"1","key":"2022111016254146800_bib36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.cmet.2008.11.009","article-title":"Hypoxia-independent angiogenesis in adipose tissues during cold acclimation","volume":"9","author":"Xue","year":"2009","journal-title":"Cell Metab"},{"key":"2022111016254146800_bib37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fendo.2015.00039","article-title":"The hypoxia-inducible factor pathway in adipocytes: the role of HIF-2 in adipose inflammation and hypertrophic cardiomyopathy","volume":"6","author":"Lin","year":"2015","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"12","key":"2022111016254146800_bib38","doi-asserted-by":"crossref","first-page":"1903366","DOI":"10.1002\/advs.201903366","article-title":"Transferrin receptor 1 regulates thermogenic capacity and cell fate in brown\/beige adipocytes","volume":"7","author":"Li","year":"2020","journal-title":"Adv Sci (Weinh)"},{"issue":"4","key":"2022111016254146800_bib39","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2174\/22124063MTEwlMzgAy","article-title":"Updated understanding of platelets in thrombosis and hemostasis: the roles of integrin PSI domains and their potential as therapeutic targets","volume":"20","author":"Mackeigan","year":"2020","journal-title":"Cardiovasc Hematol Disord Drug Targets"},{"issue":"3","key":"2022111016254146800_bib40","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1473-0502(03)00044-2","article-title":"Platelets in hemostasis and\u00a0thrombosis: role of integrins and their ligands","volume":"28","author":"Ni","year":"2003","journal-title":"Transfus Apher Sci"},{"issue":"6","key":"2022111016254146800_bib41","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/10408363.2016.1200008","article-title":"Platelets are versatile cells: new discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond","volume":"53","author":"Xu","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"issue":"5","key":"2022111016254146800_bib42","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1055\/s-0038-1641566","article-title":"Hypobaric hypoxia causes elevated thrombin generation mediated by FVIII that is balanced by decreased platelet activation","volume":"118","author":"Kicken","year":"2018","journal-title":"Thromb Haemost"},{"issue":"3","key":"2022111016254146800_bib43","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1182\/blood.V126.23.3549.3549","article-title":"Hypobaric hypoxia induces hypercoagulability due to an increase in microparticles","volume":"126","author":"Kicken","year":"2015","journal-title":"Blood"},{"issue":"6","key":"2022111016254146800_bib44","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/09537100903116516","article-title":"Effect of prolonged stay at high altitude on platelet aggregation and fibrinogen levels","volume":"20","author":"Vij","year":"2009","journal-title":"Platelets"},{"issue":"2","key":"2022111016254146800_bib45","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1152\/japplphysiol.00991.2005","article-title":"Platelet count and function at high altitude and in high-altitude pulmonary edema","volume":"100","author":"Lehmann","year":"2006","journal-title":"J\u00a0Appl Physiol"},{"issue":"4","key":"2022111016254146800_bib46","doi-asserted-by":"crossref","first-page":"e93218","DOI":"10.1371\/journal.pone.0093218","article-title":"Platelet dynamics during natural and pharmacologically induced torpor and forced hypothermia","volume":"9","author":"de Vrij","year":"2014","journal-title":"PLoS One"},{"issue":"9","key":"2022111016254146800_bib47","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1093\/ajh\/2.9.724","article-title":"Acute effects of exposure to cold on blood pressure, platelet function and sympathetic nervous activity in humans","volume":"2","author":"Kawahara","year":"1989","journal-title":"Am J Hypertens"},{"issue":"1","key":"2022111016254146800_bib48","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1161\/STROKEAHA.117.017838","article-title":"Ambient temperature and stroke risk: evidence supporting a short-term effect at a population level from acute environmental exposures","volume":"49","author":"Lavados","year":"2018","journal-title":"Stroke"},{"issue":"10","key":"2022111016254146800_bib49","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1111\/jth.14555","article-title":"Hypothermia-induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model","volume":"17","author":"Horioka","year":"2019","journal-title":"J\u00a0Thromb Haemost"},{"issue":"9","key":"2022111016254146800_bib50","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1182\/blood.2019000200","article-title":"TNF-\u03b1-driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging","volume":"134","author":"Davizon-Castillo","year":"2019","journal-title":"Blood"},{"key":"2022111016254146800_bib51","doi-asserted-by":"crossref","first-page":"18","DOI":"10.21037\/aob-20-32","article-title":"Aging, chronic inflammation, and platelet hyperactivity","volume":"5","author":"Ma","year":"2020","journal-title":"Ann Blood"},{"issue":"1","key":"2022111016254146800_bib52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/09537104.2019.1572876","article-title":"The human platelet transcriptome and proteome is altered and pro-thrombotic functional responses are increased during prolonged hypoxia exposure at high altitude","volume":"31","author":"Shang","year":"2020","journal-title":"Platelets"},{"issue":"4","key":"2022111016254146800_bib53","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.coph.2013.04.009","article-title":"Targeting the HIF pathway in inflammation and immunity","volume":"13","author":"Scholz","year":"2013","journal-title":"Curr Opin Pharmacol"},{"issue":"32","key":"2022111016254146800_bib54","doi-asserted-by":"crossref","first-page":"20055","DOI":"10.1074\/jbc.272.32.20055","article-title":"Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1","volume":"272","author":"Rolfs","year":"1997","journal-title":"J\u00a0Biol Chem"},{"issue":"6","key":"2022111016254146800_bib55","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1089\/ars.2020.8148","article-title":"NRF2 and hypoxia inducible factors: key players in the redox control of systemic iron homeostasis","volume":"35","author":"Duarte","year":"2021","journal-title":"Antioxid Redox Signal"},{"key":"2022111016254146800_bib56","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.3389\/fphys.2018.01949","article-title":"Acute mountain sickness is associated with a high ratio of endogenous testosterone to estradiol after high-altitude exposure at 3,700 m in young Chinese men","volume":"9","author":"Ding","year":"2019","journal-title":"Front Physiol"},{"issue":"34","key":"2022111016254146800_bib57","doi-asserted-by":"crossref","first-page":"24147","DOI":"10.1074\/jbc.274.34.24147","article-title":"Identification of a functional hypoxia-response element in the transferrin-receptor gene","volume":"274","author":"Lok","year":"1999","journal-title":"J\u00a0Biol Chem"},{"issue":"34","key":"2022111016254146800_bib58","doi-asserted-by":"crossref","first-page":"24142","DOI":"10.1074\/jbc.274.34.24142","article-title":"Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific posttranscriptional regulation","volume":"274","author":"Tacchini","year":"1999","journal-title":"J\u00a0Biol Chem"},{"issue":"3","key":"2022111016254146800_bib59","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3409\/fb63_3.221","article-title":"Comparison of selected morphological, rheological and biochemical parameters of winter swimmers' blood at the end of one winter swimming season and at the beginning of another","volume":"63","author":"Teleglow","year":"2015","journal-title":"Folia Biologica (Krakow)"},{"issue":"4","key":"2022111016254146800_bib60","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1182\/blood-2018-04-841585","article-title":"Hypoxia downregulates protein S expression","volume":"132","author":"Pilli","year":"2018","journal-title":"Blood"},{"issue":"14","key":"2022111016254146800_bib61","doi-asserted-by":"crossref","first-page":"8298","DOI":"10.1073\/pnas.95.14.8298","article-title":"Tissue factor transcription driven by Egr-1 is a critical mechanism of murine pulmonary fibrin deposition in hypoxia","volume":"95","author":"Yan","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"2022111016254146800_bib62","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1182\/blood-2018-06-854976","article-title":"Hypoxia and thrombosis","volume":"132","author":"Prchal","year":"2018","journal-title":"Blood"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/140\/19\/2063\/1929427\/blood_bld-2022-016410-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/140\/19\/2063\/1929427\/blood_bld-2022-016410-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T11:26:30Z","timestamp":1668079590000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/140\/19\/2063\/486448\/Hypoxia-and-low-temperature-upregulate-transferrin"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,10]]},"references-count":62,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2022,11,10]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2022016410","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,10]]}}}