| First Author | Ye Z | Year | 2019 |
| Journal | Cell Death Dis | Volume | 10 |
| Issue | 7 | Pages | 507 |
| PubMed ID | 31263109 | Mgi Jnum | J:294406 |
| Mgi Id | MGI:6456299 | Doi | 10.1038/s41419-019-1736-5 |
| Citation | Ye Z, et al. (2019) The P-selectin and PSGL-1 axis accelerates atherosclerosis via activation of dendritic cells by the TLR4 signaling pathway. Cell Death Dis 10(7):507 |
| abstractText | P-selectin and dendritic cells (DCs) are associated with atherosclerosis. However, their interactions in this setting are undefined. Herein, we investigated the role of P-selectin and its receptor P-selectin glycoprotein ligand (PSGL)-1 on atherosclerosis via activation of DCs. In the current study, a total of 34 patients with ST elevation myocardial infarction (STEMI) and 34 healthy control subjects were enrolled. Serum concentration of P-selectin was higher and the myeloid DC/plasmacytoid DC (mDC/pDC) ratio was lower in STEMI patients than in normal individuals. Interestingly, in STEMI patients, P-selectin was decreased and the mDC/pDC ratio was increased at 5-7 days after successful percutaneous coronary intervention, as compared with values on admission. Serum P-selectin was inversely correlated with the mDC/pDC ratio. Moreover, ApoE(-/-)P(-/-) and ApoE(-/-)PSGL-1(-/-) mice developed small atherosclerotic plaques after feeding of a western diet for 12 weeks and DC infiltration was significantly reduced. P-selectin stimulation markedly induced phenotypic maturation, enhanced secretion of inflammatory cytokines, communication with T cells, and the adhesion and migration of DCs. In vivo, DC maturation was significantly attenuated in P-selectin and PSGL1 knockout mice under hypercholesterolemic and inflammatory conditions. These effects were associated with the activation of myeloid differentiation primary response 88 (MYD88)-dependent and MyD88-independent Toll-like receptor 4 (TLR4) signaling pathways. Taken together, binding of P-selectin to PSGL-1 on DCs contributes to atherosclerosis progression via DC activation via the TLR4 signaling pathway. |
