Estudios científicos
Shear stress preconditioning modulates endothelial susceptibility to circulating TNF-alpha and monocytic cell recruitment in a simplified model of arterial bifurcations
Abstract:
OBJECTIVE: Atherosclerotic plaque formation results from a combination of local shear stress patterns and inflammatory processes. This study investigated the endothelial response to shear stress in combination with the inflammatory cytokine TNF-alpha in a simplified model of arterial bifurcation. METHODS: Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by stimulation with TNF-alpha. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Endothelial protein expression was determined by immunofluorescence. RESULTS: Adhesion of monocytic cells to unstimulated ECs was nearly undetectable under laminar shear stress and was slightly increased under non-uniform shear stress. Exposure of ECs to non-uniform shear stress in combination with TNF-alpha induced a 12-fold increase in monocytic cell recruitment and a significant induction of endothelial E-selectin and VCAM-1 expression. Both these effects were prevented in ECs exposed to laminar shear stress. The significant differences in TNF-alpha-induced monocytic cell recruitment and adhesion molecule expression between laminar and non-uniform shear stress regions were abolished in the absence of shear stress preconditioning. Simvastatin (1 micromol/L) suppressed the non-uniform shear stress- and TNF-alpha-induced increase in monocytic cell adhesion by about 30% via inhibition of VCAM-1 expression. Resveratrol, the active component of red wine, inhibited the expression of both VCAM-1 and E-selectin, and reduced monocytic cell recruitment by 50% at 20 micromol/L. CONCLUSIONS: Non-uniform shear stress induces endothelial susceptibility to circulating TNF-alpha and adhesion of monocytic cells. Interference with this process may inhibit inflammatory response in atherosclerosis-prone regions.
Comentarios divulgativos:
La formación de la placa aterogénica resulta de la combinación de porcesos debidos al daño sufrido en el endotelio y a la inflamación. En este estudio se investiga la respuesta endotelial al daño endotelial en convinación con la citokina TNF-alfa en un modelo simple de bifurcación arterial. Para ello células del endotelio de las venas umbilicales fueron expuestas a daño endotelial saeguido de estimulación por el factor TNF-alfa. Para poder estudiar la la adhesión celular estas células fueron perfundidas con medio que contenía células monocíticas TPH-1.Se observó que el resveratrol, el cual es un componente del vino tinto, inhibia la expresión de VCAM-1 y Selectina-E y reducía el reclutamiento monocítico en un 50% a 20 micromoles/L. El daño endotelial induce la susceptibilidad a la circulación del factor TNF-alfa y la adesión de células monocíticas. Las interferencias en este proceso pueden inhibir la respuesta inflamatoria en las regiones con aterosclerosis
