Evaluation of circulating nucleosomes and the protective effect of sinvastatin on neutrophil activation in patients with venous thromboembolism

• Grant number: 13/26244-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2014
• End date: December 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Fernanda Loureiro de Andrade Orsi
• Grantee: Fernanda Loureiro de Andrade Orsi
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Joyce Maria Annichino-Bizzacchi

Abstract

The association between thrombosis and inflammation has been studied mainly based on the participation of neutrophils on animal models of thrombosis, nevertheless, the participation of this cells in the physiopathology of venous thromboembolism (VTE) in humans is not established. A key point during the inflammatory response is the leucocytes migration to the inflammation sites through the adhesion to the endothelial cells. The adhesion to endothelial cells and diapedesis to the inflammation site are mediated by the interaction of distinct cellular adhesion molecules (CAMs), such as selectins, integrins and ligands. The neutrophil recruitment processes includes the selectin mediated rolling, neutrophil activation and ²2-integrin mediated adhesion and diapedesis. Recently, its has been recognized that neutrophil activation leads to the formation of neutrophils extracellular traps (NET), and the exposure of nucleosomes on these NETs contribute to coagulation activation in vivo and development of VTE in animal models. The aim of this study is to evaluate in patients the association of VET, and its sequels, with the activation of neutrophils. The neutrophils adhesive and chemotatic properties, the quantification of circulating nucleosome as a marker of NETs formation, and the presence of reactive oxygen species (ROS) will be determined in patients with VTE. The protective effect of sinvastatin on neutrophil activation will also be determined in vitro. Undertanding the role of neutrophils on the physiopathology of VTE may ultimately contribute for new therapeutic strategies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZAPPONI, KIARA C. S.; ORSI, FERNANDA A.; CUNHA, JOSE LUIZ R.; DE BRITO, INGRID R.; ROMANO, ANNA VIRGINIA C.; BITTAR, LUIS FERNANDO; DE PAULA, ERICH VINICIUS; PENTEADO, CARLA F.; MONTALVAO, SILMARA; ANNICHINO-BIZZACCHI, JOYCE MARIA. Neutrophil activation and circulating neutrophil extracellular traps are increased in venous thromboembolism patients for at least one year after the clinical event. JOURNAL OF THROMBOSIS AND THROMBOLYSIS, v. 53, n. 1, AUG 2021. (13/26244-3, 13/22981-3, 16/14172-6)