Oxidized LDL-bound CD36 recruits an Naâº/Kâº-ATPase-Lyn complex in macrophages that promotes atherosclerosis.
Sci Signal
; 8(393): ra91, 2015 Sep 08.
Article
en En
| MEDLINE
| ID: mdl-26350901
ABSTRACT
One characteristic of atherosclerosis is the accumulation of lipid-laden macrophage foam cells in the arterial wall. We have previously shown that the binding of oxidized low-density lipoprotein (oxLDL) to the scavenger receptor CD36 activates the kinase Lyn, initiating a cascade that inhibits macrophage migration and is necessary for foam cell generation. We identified the plasma membrane ion transporter Na(+)/K(+)-ATPase as a key component in the macrophage oxLDL-CD36 signaling axis. Using peritoneal macrophages isolated from Atp1a1 heterozygous or Cd36-null mice, we demonstrated that CD36 recruited an Na(+)/K(+)-ATPase-Lyn complex for Lyn activation in response to oxLDL. Macrophages deficient in the α1 Na(+)/K(+)-ATPase catalytic subunit did not respond to activation of CD36, showing attenuated oxLDL uptake and foam cell formation, and oxLDL failed to inhibit migration of these macrophages. Furthermore, Apoe-null mice, which are a model of atherosclerosis, were protected from diet-induced atherosclerosis by global deletion of a single allele encoding the α1 Na(+)/K(+)-ATPase subunit or reconstitution with macrophages that lacked an allele encoding the α1 Na(+)/K(+)-ATPase subunit. These findings identify Na(+)/K(+)-ATPase as a potential target for preventing or treating atherosclerosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ATPasa Intercambiadora de Sodio-Potasio
/
Familia-src Quinasas
/
Antígenos CD36
/
Aterosclerosis
/
Lipoproteínas LDL
/
Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Signal
Asunto de la revista:
CIENCIA
/
FISIOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos