Neutrophil extracellular trap regulators in sickle cell disease: Modulation of gene expression of PADI4, neutrophil elastase, and myeloperoxidase during vaso‐occlusive crisis

Recent evidence suggests that generation of neutrophil extracellular traps (NETosis), one of the components of immunothrombosis, is associated with the pathogenesis of both venous thromboembolism and sickle cell disease (SCD). NETosis is a complex process regulated by several proteins such as peptid...

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Vydáno v:Research and practice in thrombosis and haemostasis Ročník 5; číslo 1; s. 204 - 210
Hlavní autoři: Hounkpe, Bidossessi Wilfried, Chenou, Francine, Domingos, Igor de Farias, Cardoso, Evilazio Cunha, Costa Sobreira, Marcondes José de Vasconcelos, Araujo, Aderson S., Lucena‐Araújo, Antonio Roberto, da Silva Neto, Pedro Vieira, Malheiro, Adriana, Fraiji, Nelson Abrahim, Costa, Fernando Ferreira, Bezerra, Marcos André C., Santos, Magnun Nueldo Nunes, De Paula, Erich Vinicius
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 01.01.2021
Elsevier Limited
John Wiley and Sons Inc
Elsevier
Témata:
Anticoagulants
Blood
Blood platelets
Brief Report
elastase
Gene expression
Genotype & phenotype
Granulocytes
Hematology
Hemoglobin
Laboratories
neutrophil extracellular traps
Neutrophils
Original ‐ Thrombosis
Pathogenesis
Pathogens
peptidylarginine deiminase 4
Plasma
Sickle cell disease
Statistical analysis
vaso‐occlusive crisis
United States > US
elastase
vaso‐occlusive crisis
neutrophil extracellular traps
peptidylarginine deiminase 4
sickle cell disease
ISSN:2475-0379, 2475-0379
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Shrnutí:Recent evidence suggests that generation of neutrophil extracellular traps (NETosis), one of the components of immunothrombosis, is associated with the pathogenesis of both venous thromboembolism and sickle cell disease (SCD). NETosis is a complex process regulated by several proteins such as peptidyl arginine deaminase 4 (PADI4), neutrophil elastase (ELANE), and myeloperoxidase (MPO). Among these regulators, PADI4 is responsible of histone citrullination, an essential step for NETosis. Accordingly, its inhibition has been recently cited as a promising therapeutic strategy for diseases such as SCD. Although attractive, this strategy requires supportive evidence of its role in the pathogenesis of SCD. Patients from two independent cohorts were enrolled in this study. Samples were obtained at steady state (53 patients) or during acute episodes of vaso‐occlusive crisis (VOC; 28 patients) in patients from cohort 1. mRNA was extracted from granulocytes to analyze PADI4, ELANE, and MPO expression by qPCR. Furthermore, plasma activity of PADI4 was assessed from an independent cohort in 15 patients, within 24 hours from admission for VOC. Race‐matched healthy individuals from the same geographic regions were used as controls for each cohort. Higher levels of gene expression of PADI4 and ELANE were observed during VOC. Furthermore, plasma activity of PADI4 was higher in acute VOC when compared to healthy individuals. These results demonstrate that NETosis regulators are modulated during acute VOC, and pave the way for studies of PADI4 inhibition as a therapeutic strategy for acute VOC in SCD.
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SourceType-Scholarly Journals-1
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Funding informationThis study was financially supported by the Sao Paulo Research Foundation. grants # 2014/00984‐3; 2015/24666‐3 and 2016/14172‐6; CNPq Brazil, grant # 309317/2016; and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior – Brasil. (CAPES) ‐ Finance Code 001.
Handling Editor: Dr Pantep Angchaisuksiri.
ISSN:2475-0379
2475-0379
DOI:10.1002/rth2.12463