Inflammasome activation promotes venous thrombosis through pyroptosis

Yan Zhang, Jian Cui, Guoying Zhang, Congqing Wu, Ahmed Abdel-Latif, Susan S. Smyth, Toshihiko Shiroishi, Nigel Mackman, Yinan Wei, Min Tao, Zhenyu Li

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Crosstalk between coagulation and innate immunity contributes to the progression of many diseases, including infection and cardiovascular disease. Venous thromboembolism (VTE), including pulmonary embolism and deep vein thrombosis (DVT), is among the most common causes of cardiovascular death. Here, we show that inflammasome activation and subsequent pyroptosis play an important role in the development of venous thrombosis. Using a flow restriction induced mouse venous thrombosis model in the inferior vena cava (IVC), we show that deficiency of caspase-1, but not caspase-11, protected against flow restriction induced thrombosis. Interleukin-1b expression increased in the IVC following ligation, indicating that inflammasome is activated during injury. Deficiency of gasdermin D (GSDMD), an essential mediator of pyroptosis, protected against restriction-induced venous thrombosis. After induction of venous thrombosis, fibrin was deposited in the veins of wild-Type mice, as detected using immunoblotting with a monoclonal antibody that specifically recognizes mouse fibrin, but not in the caspase-1 deficient or GSDMD-deficient mice. Depletion of macrophages by gadolinium chloride or deficiency of tissue factor also protected against venous thrombosis. Our data reveal that tissue factor released from pyroptotic monocytes and macrophages following inflammasome activation triggers thrombosis.

Original languageEnglish
Pages (from-to)2619-2623
Number of pages5
JournalBlood advances
Volume5
Issue number12
DOIs
StatePublished - Jun 22 2021

Bibliographical note

Publisher Copyright:
© 2021 American Society of Hematology. All rights reserved.

ASJC Scopus subject areas

  • Hematology

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