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Complement activation is involved in the development of TA\u2010TMA. However, the underlying mechanism is unclear. Therefore, 21 samples of TA\u2010TMA and 1:1 matched controls were measured for hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) and complement protein. The mechanism was investigated both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. In this study, we found that levels of HIF\u20101\u03b1 were significantly higher in TA\u2010TMA patients than that in non\u2010TA\u2010TMA controls. Upregulation of HIF\u20101\u03b1 induced an increase in membrane\u2010bound complement C3 and dysfunction of human umbilical vein endothelial cells (HUVECs) <jats:italic>in vitro<\/jats:italic>. Increasing HIF\u20101\u03b1 <jats:italic>in vivo<\/jats:italic> led to C3 and C5b\u20109 deposition in the glomerular endothelial capillary complex, thrombocytopenia, anaemia, and increased serum lactate dehydrogenase (LDH) levels in wild\u2010type (WT) but not in <jats:italic>C3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice subjected to HSCT. High platelet aggregation in peripheral blood and CD41\u2010positive microthrombi in the kidney were also found in dimethyloxallyl glycine (DMOG)\u2010treated mice, recapitulating the TA\u2010TMA phenotype seen in patients. Comprehensive analysis, including DNA array, luciferase reporter assay, chromatin immunoprecipitation (ChIP)\u2010seq, and quantitative polymerase chain reaction (PCR), revealed that HIF\u20101\u03b1 interacted with the promoter of complement factor H (CFH) to inhibit its transcription. Decreased CFH led to complement activation in endothelial cells.<\/jats:p>","DOI":"10.1111\/bjh.18377","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T06:01:49Z","timestamp":1658469709000},"page":"603-615","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Upregulation of <scp>HIF<\/scp>\u20101\u03b1 contributes to complement activation in transplantation\u2010associated thrombotic microangiopathy"],"prefix":"10.1111","volume":"199","author":[{"given":"Jiaqian","family":"Qi","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology The First Affiliated Hospital of Soochow University  Suzhou China"},{"name":"Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology Soochow University  Suzhou China"},{"name":"Key Laboratory of Thrombosis and Hemostasis of Ministry of 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