HIF-1α is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium.
Elife
; 62017 05 30.
Article
en En
| MEDLINE
| ID: mdl-28556776
Hemodynamic forces regulate vascular functions. Disturbed flow (DF) occurs in arterial bifurcations and curvatures, activates endothelial cells (ECs), and results in vascular inflammation and ultimately atherosclerosis. However, how DF alters EC metabolism, and whether resulting metabolic changes induce EC activation, is unknown. Using transcriptomics and bioenergetic analysis, we discovered that DF induces glycolysis and reduces mitochondrial respiratory capacity in human aortic ECs. DF-induced metabolic reprogramming required hypoxia inducible factor-1α (HIF-1α), downstream of NAD(P)H oxidase-4 (NOX4)-derived reactive oxygen species (ROS). HIF-1α increased glycolytic enzymes and pyruvate dehydrogenase kinase-1 (PDK-1), which reduces mitochondrial respiratory capacity. Swine aortic arch endothelia exhibited elevated ROS, NOX4, HIF-1α, and glycolytic enzyme and PDK1 expression, suggesting that DF leads to metabolic reprogramming in vivo. Inhibition of glycolysis reduced inflammation suggesting a causal relationship between flow-induced metabolic changes and EC activation. These findings highlight a previously uncharacterized role for flow-induced metabolic reprogramming and inflammation in ECs.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Flujo Sanguíneo Regional
/
Endotelio Vascular
/
Regulación de la Expresión Génica
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos