| First Author | Chen Y | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 393 | Pages | ra91 |
| PubMed ID | 26350901 | Mgi Jnum | J:259992 |
| Mgi Id | MGI:6141769 | Doi | 10.1126/scisignal.aaa9623 |
| Citation | Chen Y, et al. (2015) Oxidized LDL-bound CD36 recruits an Na(+)/K(+)-ATPase-Lyn complex in macrophages that promotes atherosclerosis. Sci Signal 8(393):ra91 |
| abstractText | 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 alpha1 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 alpha1 Na(+)/K(+)-ATPase subunit or reconstitution with macrophages that lacked an allele encoding the alpha1 Na(+)/K(+)-ATPase subunit. These findings identify Na(+)/K(+)-ATPase as a potential target for preventing or treating atherosclerosis. |
