PMID- 31263109 OWN - NLM STAT- MEDLINE DCOM- 20200713 LR - 20210110 IS - 2041-4889 (Electronic) VI - 10 IP - 7 DP - 2019 Jul 1 TI - The P-selectin and PSGL-1 axis accelerates atherosclerosis via activation of dendritic cells by the TLR4 signaling pathway. PG - 507 LID - 10.1038/s41419-019-1736-5 [doi] LID - 507 AB - 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. FAU - Ye, Zhishuai AU - Ye Z AUID- ORCID: 0000-0002-8446-1749 AD - Cardiac Center/Division of Cardiovascular Diseases, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. AD - Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China. FAU - Zhong, Lei AU - Zhong L AD - Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China. FAU - Zhu, Shengnan AU - Zhu S AD - Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China. FAU - Wang, Yinuo AU - Wang Y AD - Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China. FAU - Zheng, Jie AU - Zheng J AD - Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China. FAU - Wang, Shujing AU - Wang S AD - Department of Biochemistry and Molecular Biology, Dalian Medical University, 116044, Dalian, China. FAU - Zhang, Jianing AU - Zhang J AD - College of Life Sciences and Pharmacy, Dalian University of Technology, 116027, Dalian, China. FAU - Huang, Rongchong AU - Huang R AUID- ORCID: 0000-0002-2607-2112 AD - Cardiac Center/Division of Cardiovascular Diseases, Beijing Friendship Hospital, Capital Medical University, 100050, Beijing, China. rchuang@ccmu.edu.cn. AD - Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 116011, Dalian, China. rchuang@ccmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190701 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Apolipoproteins E) RN - 0 (B7-2 Antigen) RN - 0 (Membrane Glycoproteins) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (P-Selectin) RN - 0 (P-selectin ligand protein) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Aged MH - Animals MH - Apolipoproteins E/genetics/metabolism MH - Atherosclerosis/genetics/*metabolism MH - B7-2 Antigen/metabolism MH - Dendritic Cells/*metabolism MH - Female MH - Humans MH - Male MH - Membrane Glycoproteins/genetics/*metabolism MH - Mice, Knockout MH - Middle Aged MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - P-Selectin/genetics/*metabolism MH - Signal Transduction/genetics/physiology MH - Toll-Like Receptor 4/genetics/*metabolism PMC - PMC6602970 COIS- The authors declare that they have no conflict of interest. EDAT- 2019/07/03 06:00 MHDA- 2020/07/14 06:00 PMCR- 2019/07/01 CRDT- 2019/07/03 06:00 PHST- 2019/01/24 00:00 [received] PHST- 2019/06/06 00:00 [accepted] PHST- 2019/06/05 00:00 [revised] PHST- 2019/07/03 06:00 [entrez] PHST- 2019/07/03 06:00 [pubmed] PHST- 2020/07/14 06:00 [medline] PHST- 2019/07/01 00:00 [pmc-release] AID - 10.1038/s41419-019-1736-5 [pii] AID - 1736 [pii] AID - 10.1038/s41419-019-1736-5 [doi] PST - epublish SO - Cell Death Dis. 2019 Jul 1;10(7):507. doi: 10.1038/s41419-019-1736-5.