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Evaluation of circulating nucleosomes and influence of Simvastatin in vitro in the adhesive and chemotactic properties of neutrophils in patients with venous thromboembolism

Grant number: 13/22981-3
Support Opportunities:Scholarships in Brazil - Doctorate
Start date: March 01, 2014
End date: May 16, 2016
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Joyce Maria Annichino-Bizzacchi
Grantee:Kiara Cristina Senger Zapponi Cerri
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Despite the link between inflammation and thrombosis be known , this relationship has been most commonly explored in studies on the interactions of inflammatory cytokines and the coagulation cascade . Indeed inflammatory cells such as neutrophils , has been further explored in studies in animal models of thrombosis , but the pathophysiological mechanisms involved in this process are not yet fully defined in patients with venous thromboembolism ( VTE ) . It is known that a key event during the inflammatory process is the recruitment of leukocytes at sites of inflammation , which is often initiated by adhesion to the endothelium . Adhesion to the endothelium and infiltration of these cells in areas of inflammation are mediated by interactions of several families of cell adhesion molecules ( CAMs ) including the selectins , integrins and their ligands. The neutrophils to interact with inflamed endothelium using selectins and subsequently bind to specific sites in the vasculature through the ²2 integrin expressed on its membrane . Currently it has been argued that the activation of neutrophils also leads to formation of neutrophil extracellular networks ( NETs ) , and exposure of nucleosomes on these NETs , contributing to the activation of coagulation in vivo and the development of VTE in an animal model . Additionally, sinvastatin for the prevention of this disease has been much discussed , but their pleiotropic effects are not clear-cut . Therefore , in this paper we intend to evaluate the circulating nucleosomes as a marker of NETs in vitro and the influence of simvastatin on the chemotactic and adhesive properties of neutrophils in patients with VTE and controls in order to better understand the role of this cell in the pathophysiological process of the disease, which may have implications for the treatment and prevention of disease.

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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, . (13/26244-3, 13/22981-3, 16/14172-6)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CERRI, Kiara Cristina Senger Zapponi. Evaluation of circulating nucleosomes and influence of simvastatin IN VITRO in the adhesive and chemotactic properties of neutrophils in patients with venous thromboembolism. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.