Disturbed Cyclical Stretch of Endothelial Cells Promotes Nuclear Expression of the Pro-Atherogenic Transcription Factor NF-κB.
Ann Biomed Eng
; 45(4): 898-909, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-27796516
ABSTRACT
Exposure of endothelial cells to low and multidirectional blood flow is known to promote a pro-atherogenic phenotype. The mechanics of the vessel wall is another important mechano-stimulus within the endothelial cell environment, but no study has examined whether changes in the magnitude and direction of cell stretch can be pro-atherogenic. Herein, we developed a custom cell stretching device to replicate the in vivo stretch environment of the endothelial cell and examined whether low and multidirectional stretch promote nuclear translocation of NF-κB. A fluid-structure interaction model of the device demonstrated a nearly uniform strain within the region of cell attachment and a negligible magnitude of shear stress due to cyclical stretching of the cells in media. Compared to normal cyclical stretch, a low magnitude of cyclical stretch or no stretch caused increased expression of nuclear NF-κB (p = 0.09 and p < 0.001, respectively). Multidirectional stretch also promoted significant nuclear NF-κB expression, comparable to the no stretch condition, which was statistically higher than the low (p < 0.001) and normal (p < 0.001) stretch conditions. This is the first study to show that stretch conditions analogous to atherogenic blood flow profiles can similarly promote a pro-atherogenic endothelial cell phenotype, which supports a role for disturbed vessel wall mechanics as a pathological cell stimulus in the development of advanced atherosclerotic plaques.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Mecánico
/
Núcleo Celular
/
Regulación de la Expresión Génica
/
FN-kappa B
/
Células Endoteliales
/
Aterosclerosis
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Ann Biomed Eng
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido