Your browser doesn't support javascript.
loading
HMGB1 down-regulation mediates terameprocol vascular anti-proliferative effect in experimental pulmonary hypertension.
Nogueira-Ferreira, Rita; Ferreira-Pinto, Manuel J; Silva, Ana Filipa; Vitorino, Rui; Justino, Joana; Costa, Raquel; Moreira-Gonçalves, Daniel; Quignard, Jean-François; Ducret, Thomas; Savineau, Jean-Pierre; Leite-Moreira, Adelino F; Ferreira, Rita; Henriques-Coelho, Tiago.
Afiliación
  • Nogueira-Ferreira R; QOPNA, Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
  • Ferreira-Pinto MJ; Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal.
  • Silva AF; Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal.
  • Vitorino R; Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal.
  • Justino J; Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal.
  • Costa R; iBiMED, Departamento de Ciências Médicas, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
  • Moreira-Gonçalves D; QOPNA, Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.
  • Quignard JF; Departamento de Bioquímica, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal.
  • Ducret T; Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, Porto, Portugal.
  • Savineau JP; CIAFEL, Faculdade de Desporto, Universidade do Porto, Porto, Portugal.
  • Leite-Moreira AF; Université Bordeaux Segalen, Bordeaux, France.
  • Ferreira R; Inserm, Centre de Recherche Cardio-Thoracique, Bordeaux, France.
  • Henriques-Coelho T; Université Bordeaux Segalen, Bordeaux, France.
J Cell Physiol ; 232(11): 3128-3138, 2017 Nov.
Article en En | MEDLINE | ID: mdl-28036116
Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis. Pulmonary artery smooth muscle cells (PASMCs) play a crucial role in PAH pathophysiology, displaying a hyperproliferative, and apoptotic-resistant phenotype. In the present study, we evaluated the potential therapeutic role of terameprocol (TMP), an inhibitor of cellular proliferation and promoter of apoptosis, in a well-established pre-clinical model of PAH induced by monocrotaline (MCT) and studied the biological pathways modulated by TMP in PASMCs. Wistar rats injected with MCT or saline (SHAM group) were treated with TMP or vehicle. On day 21 after injection, we assessed bi-ventricular hemodynamics and cardiac and pulmonary morphometry. The effects of TMP on PASMCs were studied in a primary culture isolated from SHAM and MCT-treated rats, using an iTRAQ-based proteomic approach to investigate the molecular pathways modulated by this drug. In vivo, TMP significantly reduced pulmonary and cardiac remodeling and improved cardiac function in PAH. In vitro, TMP inhibited proliferation and induced apoptosis of PASMCs. A total of 65 proteins were differentially expressed in PASMCs from MCT rats treated with TMP, some of which involved in the modulation of transforming growth factor beta pathway and DNA transcription. Anti-proliferative effect of TMP seems to be explained, at least in part, by the down-regulation of the transcription factor HMGB1. Our findings support the beneficial role of TMP in PAH and suggest that it may be an effective therapeutic option to be considered in the clinical management of PAH.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Masoprocol / Proteína HMGB1 / Miocitos del Músculo Liso / Proliferación Celular / Remodelación Vascular / Hipertensión / Músculo Liso Vascular / Antihipertensivos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cell Physiol Año: 2017 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Masoprocol / Proteína HMGB1 / Miocitos del Músculo Liso / Proliferación Celular / Remodelación Vascular / Hipertensión / Músculo Liso Vascular / Antihipertensivos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Cell Physiol Año: 2017 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Estados Unidos