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Visualizing TGF-ß and BMP signaling in human atherosclerosis: a histological evaluation based on Smad activation.
van Dijk, R A; Engels, C C; Schaapherder, A F; Mulder-Stapel, A; Ten Dijke, P; Hamming, J F; Lindeman, J H N.
Afiliación
  • van Dijk RA; Department of Vascular Surgery, Leiden University Medical Center, Leiden, Netherlands.
Histol Histopathol ; 27(3): 387-96, 2012 03.
Article en En | MEDLINE | ID: mdl-22237716
BACKGROUND: The TGF-ß superfamily members transforming growth factor-ß (TGF-ß/Activin) and bone morphogenetic proteins (BMP) have been implicated in the pathogenesis of atherosclerosis. However, their role in human disease remains controversial. In this study we used Smad phosphorylation as a read out for TGF-ß and BMP signaling during the initiation, progression and (de)stabilization of human atherosclerotic disease. MATERIAL AND METHODS: A systematic analysis was performed in 114 peri-renal aortic patches (stained with Movat Pentachrome, H&E, pSmad2, pSmad1,5,8 and PAI-1) covering the entire atherosclerotic spectrum (van Dijk, 2010). Immunostaining against T-cells (CD3) and monocytes and macrophages (CD68) was used to explore a putative association between TGF-ß and BMP signaling and vascular inflammation. RESULTS: Smad phosphorylation was present within the normal arterial wall in approximately 10% of the endothelial cells and intimal smooth muscle cells. A significant increase in pSmad2 and pSmad1,5,8 positivity was found in non-progressive lesions (>50% positivity). No further increase or decrease was found in the progressive atherosclerotic lesions, vulnerable and stabilized lesions. No association was found between TGF-ß and BMP signaling and CD3 and CD68 expression, nor cap thickness. CONCLUSION: Activation of the TGF-ß and BMP pathways is an early event in atherosclerotic lesion formation. No significant relationships were found between Smad phosphorylation and vessel wall inflammation or plaque vulnerability.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aorta / Enfermedades de la Aorta / Transducción de Señal / Factor de Crecimiento Transformador beta / Proteínas Morfogenéticas Óseas / Aterosclerosis / Proteínas Smad Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Histol Histopathol Asunto de la revista: HISTOLOGIA / PATOLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: España

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aorta / Enfermedades de la Aorta / Transducción de Señal / Factor de Crecimiento Transformador beta / Proteínas Morfogenéticas Óseas / Aterosclerosis / Proteínas Smad Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Histol Histopathol Asunto de la revista: HISTOLOGIA / PATOLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: España