english Icono del idioma   español Icono del idioma  

Por favor, use este identificador para citar o enlazar este ítem: https://hdl.handle.net/20.500.12008/21960 Cómo citar
Título: In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR–/–ApoB100/100 mice
Autor: Blanco, Fabiana
Heinonen, Suvi E.
Gurzeler, Erika
Berglund, Lisa M.
Dutius Andersson, Anna-Maria
Kotova, Olga
Jönsson-Rylander, Ann-Cathrine
Ylä-Herttuala, Seppo
Gomez, Maria F.
Tipo: Preprint
Palabras clave: Atherosclerosis, Oxidative stress, Type 2 diabetes, NFAT, Hyperglycemia, ApoB100
Fecha de publicación: 2018
Resumen: Aims: Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here we investigated the effects of Nuclear Factor of Activated T-cells (NFAT) inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease. Methods & Results: IGF-II/LDLR-/-ApoB100/100 mice were generated by crossbreeding LDL receptor deficient mice that synthesize only apolipoprotein B100 (LDLR-/-ApoB100/100) with transgenic mice over-expressing insulin-like growth factor-II (IGF-II) in pancreatic β cells. Mice have mild hyperglycemia and hyperinsulinemia, and develop complex atherosclerotic lesions. In vivo treatment with the NFAT blocker A-285222 for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the brachiocephalic artery of IGFII/ LDLR-/-ApoB100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and histologically after termination. Treatment had no impact on plaque composition (i.e. muscle, collagen, macrophages). The reduced plaque area could not be explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition of NFAT was associated with increased expression of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic vascular smooth muscle cells (VSMCs). Conclusions: Targeting the NFAT signaling pathway may be an attractive approach for the treatment of diabetic macrovascular complications.
Descripción: Versión Preprint. Publicado en : Diabetes and Vascular Disease Research, Vol. 15, no. 4, 2018, pp. 302-313 .
Citación: Blanco, F, Heinonen, S, Gurzeler, E, y otros. "In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR–/–ApoB100/100 mice" [en línea]. Preprint. Publicado en Diabetes and Vascular Disease Research, Vol. 15, no. 4, 2018, pp. 302-313 . DOI: https://doi.org/10.1177/1479164118759220
Licencia: Licencia Creative Commons (CC-BY-NC 4.0) Atribución-No Comercial
Aparece en las colecciones: Publicaciones Académicas y Científicas - Facultad de Medicina

Ficheros en este ítem:
Fichero Descripción Tamaño Formato   
Blanco et al_REVISED mans_DVDR.pdf199,99 kBAdobe PDFVisualizar/Abrir
Blanco et al Figures 1-5_comprimido.pdfAnexo245,19 kBAdobe PDFVisualizar/Abrir
Blanco et al Figure 2_comprimido.pdfAnexo146,32 kBAdobe PDFVisualizar/Abrir


Este ítem está sujeto a una licencia Creative Commons Licencia Creative Commons Creative Commons