Cytoprotective activated protein C averts Nlrp3 inflammasome–induced ischemia-reperfusion injury via mTORC1 inhibition

Author:

Nazir Sumra1,Gadi Ihsan1,Al-Dabet Moh’d Mohanad1,Elwakiel Ahmed1,Kohli Shrey1,Ghosh Sanchita1,Manoharan Jayakumar1,Ranjan Satish1,Bock Fabian12,Braun-Dullaeus Ruediger C.3,Esmon Charles T.45,Huber Tobias B.6,Camerer Eric7,Dockendorff Chris8,Griffin John H.9,Isermann Berend1,Shahzad Khurrum110

Affiliation:

1. Department of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany;

2. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;

3. Division of Cardiology and Angiology, Department of Internal Medicine, Otto-von-Guericke-University, Magdeburg, Germany;

4. Coagulation Biology Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, OK;

5. Departments of Pathology and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;

6. Department of Medicine III, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

7. INSERM U970, Paris Cardiovascular Research Centre, Paris, France;

8. Department of Chemistry, Marquette University, Milwaukee, WI;

9. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA; and

10. Department of Biotechnology, University of Sargodha, Sargodha, Pakistan

Abstract

Key Points aPC protects from myocardial and renal IRIs by restricting mTORC1-mediated activation of the Nlrp3 inflammasome. Nlrp3 inflammasome suppression by aPC is independent of its anticoagulant effect, depends on PAR-1, and can be mimicked by parmodulin-2.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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