-
Hospital Santo Amaro
Referência em obstetrícia, neonatologia e cirurgias em geral
-
IBIT
Matriz da FJS e destaque nacional no combate à tuberculose
-
Soluções em Saúde para Empresas
Referência em soluções que garantem a proteção e saúde dos trabalhadores, promovendo um ambiente seguro e sustentável para o futuro da sua empresa.
-
Laboratório José Silveira
Qualidade e excelência em análises clínicas e anatomia patológica
-
IBR
Modelo em reabilitação de casos de limitações psicomotoras
-
Hospital Cristo Redentor
Atende a demanda de partos e de emergências em Itapetinga (BA)
-
Centro de Reabilitação da Ribeira
Atendimento especializado a pacientes com deficiências
-
Hospital Geral de Itaparica
Atendimento de urgência, obstétrico e cirúrgico
-
Santa Casa de Jequié
Qualidade em assistência obstétrica e clínica em Jequié (BA)
-
Saúde e Cidadania
Programa que leva saúde e assistência social a quem mais precisa
-
NICSA - Memorial em Santo Amaro
Memorial em Santo Amaro
ABSTRACT: In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidence of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation. We validated our findings in a nonhuman primate model, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)-related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.
Comment in: Suppression of monocyte inflammatory and coagulopathy responses in HIV infection. [Ann Transl Med. 2018]
- Data de Publicação: 30/08/2017
- Autores: Schechter ME, Andrade BB, He T, Richter GH, Tosh KW, Policicchio BB, Singh A, Raehtz KD, Sheikh V, Ma D, Brocca-Cofano E, Apetrei C, Tracy R, Ribeiro RM, Sher A, Francischetti IMB, Pandrea I, Sereti I. Sci Transl Med.