Shear-Sensitive Genes in Aortic Valve Endothelium.
Antioxid Redox Signal
; 25(7): 401-14, 2016 09 01.
Article
en En
| MEDLINE
| ID: mdl-26651130
ABSTRACT
SIGNIFICANCE:
Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction. RECENT ADVANCES While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms-proteins, sugars, and membrane structures-at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-ß signaling and Wnt/ß-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD. CRITICAL ISSUES While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease. FUTURE DIRECTIONS Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401-414.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Válvula Aórtica
/
Regulación de la Expresión Génica
/
Mecanotransducción Celular
/
Resistencia al Corte
/
Endotelio
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Antioxid Redox Signal
Asunto de la revista:
METABOLISMO
Año:
2016
Tipo del documento:
Article
País de afiliación:
Georgia