Evaluation of the mechanisms of heme-induced tissue factor activation: Contribution of innate immune pathways

Author(s)

Hounkpe, Bidossessi Wilfried ; Peachazepi Moraes, Carla Roberta ; Lanaro, Carolina ; Nunes Santos, Magnun Nueldo ; Costa, Fernando Ferreira ; De Paula, Erich Vinicius

• Document type: Journal article
• Source: Experimental Biology and Medicine; v. 247, n. 17, p. 6-pg., 2022-07-01.

Abstract

Hemolytic diseases such as Sickle Cell Disease (SCD) are characterized by a natural propensity for both arterial and venous thrombosis. The ability of heme to induce tissue factor (TF) activation has been shown both in animal models of SCD, and in human endothelial cells and monocytes. Moreover, it was recently demonstrated that heme can induce coagulation activation in the whole blood of healthy volunteers in a TF-dependent fashion. Herein, we aim to further explore the cellular mechanisms by which heme induces TF-coagulation activation, using human mononuclear cells, which have been shown to be relevant to in vivo hemostasis. TF mRNA expression was evaluated by qPCR and TF procoagulant activity was evaluated using a 2-stage assay based on the generation of activated factor X (FXa). Heme was capable of inducing both TF expression and activation in a TLR4-dependent pathway. This activity was further amplified after TNF-alpha-priming. Our results provide additional details on the mechanisms by which heme is involved in the pathogenesis of hypercoagulability in hemolytic diseases. (AU)

• FAPESP's process: 15/24666-3 - Investigation of new pathophysiological mechanisms of hypercoagulability in Sickle Cell Disease
• Grantee: Bidossessi Wilfried Hounkpe
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders
• Grantee: Joyce Maria Annichino-Bizzacchi
• Support Opportunities: Research Projects - Thematic Grants