Endothelial Activation by Platelets from Sickle Cell Anemia Patients

Autor(es):Mostrar menos -

Proenca-Ferreira, Renata ^[1] ; Brugnerotto, Ana Flavia ^[1] ; Garrido, Vanessa Tonin ^[1] ; Dominical, Venina Marcela ^[1] ; Vital, Daiana Morelli ^[1] ; Reis Ribeiro, Marilene de Fatima ^[2] ; dos Santos, Melissa Ercolin ^[2] ; Traina, Fabiola ^{[1, 3]} ; Olalla-Saad, Sara T. ^[1] ; Costa, Fernando Ferreira ^[1] ; Conran, Nicola ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Sch Med, INCT Sangue, Haematol & Haemotherapy Ctr, Campinas, SP - Brazil

^[2] Childrens Ctr Hematol Invest, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Riberao Preto Med Sch, Dept Internal Med, BR-14049 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 9, n. 2 FEB 13 2014.
• Citações Web of Science: 18

Resumo

Sickle cell anemia (SCA) is associated with a hypercoagulable state. Increased platelet activation is reported in SCA and SCA platelets may present augmented adhesion to the vascular endothelium, potentially contributing to the vaso-occlusive process. We sought to observe the effects of platelets (PLTs) from healthy control (CON) individuals and SCA individuals on endothelial activation, in vitro. Human umbilical vein endothelial cells (HUVEC) were cultured, in the presence, or not, of washed PLTs from CON or steady-state SCA individuals. Supernatants were reserved for cytokine quantification, and endothelial adhesion molecules (EAM) were analyzed by flow cytometry; gene expressions of ICAM1 and genes of the NF-kappa B pathway were analyzed by qPCR. SCA PLTs were found to be more inflammatory, displaying increased adhesive properties, an increased production of IL-1 beta and a tendency towards elevated expressions of P-selectin and activated alpha(IIbb)beta(3). Following culture in the presence of SCA PLTs, HUVEC presented significant augmentations in the expressions of the EAM, ICAM-1 and E-selectin, as well as increased IL-8 production and increased ICAM1 and NFKB1 (encodes p50 subunit of NF-kappa B) gene expressions. Interestingly, transwell inserts abolished the effects of SCA PLTs on EAM expression. Furthermore, an inhibitor of the NF-kappa B pathway, BAY 11-7082, also prevented the induction of EAM expression on the HUVEC surface by SCA PLTs. In conclusion, we find further evidence to indicate that platelets circulate in an activated state in sickle cell disease and are capable of stimulating endothelial cell activation. This effect appears to be mediated by direct contact, or even adhesion, between the platelets and endothelial cells and via NF kappa B-dependent signaling. As such, activated platelets in SCD may contribute to endothelial activation and, therefore, to the vaso-occlusive process. Results provide further evidence to support the use of anti-platelet approaches in association with other therapies for SCD. (AU)

• Processo FAPESP: 08/57441-0 - Alterações clínicas, celulares e moleculares nas hemoglobinopatias e em outras anemias hemolíticas hereditárias
• Beneficiário: Fernando Ferreira Costa
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/54279-0 - Interações entre plaquetas de pacientes com anemia falciforme e culturas de células endoteliais humanas de cordão umbilical (HUVEC): avaliação in vitro da adesão de plaquetas e seu efeito na ativação endotelial
• Beneficiário: Renata Proenca Ferreira
• Linha de fomento: Bolsas no Brasil - Doutorado