P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt by Xianxian Wu & Xing Liu & Hang Yang & Qianlong Chen & Na Zhang & Yuhan Li & Xingchen Du & Xue Liu & Xiaoliang Jiang & Yideng Jiang & Zhou Zhou & Zhiwei Yang instant download

P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt by Xianxian Wu & Xing Liu & Hang Yang & Qianlong Chen & Na Zhang & Yuhan Li & Xingchen Du & Xue Liu & Xiaoliang Jiang & Yideng Jiang & Zhou Zhou & Zhiwei Yang instant download

AbstractPurpose P-selectin glycoprotein ligand-1 (PSGL-1) acts as a crucial regulator for the inflammatory cells infiltration by mediatingthe adhesion of leukocytes. However, the role of PSGL-1 in aortic aneurysm remains elusive. Here, we investigated the role ofPSGL-1 in aortic aneurysm (AA) development.Methods We first detected PSGL-1 expression in samples from aortic aneurysm patients and mouse AA models via westernblotting, immunofluorescence, and flow cytometry, and then we used global PSGL-1 knockout mice and their wild type controlsto establish an aortic aneurysm model induced by deoxycorticosterone acetate (DOCA) plus high salt (HS). The incidence, fatalityrates, and the pathological changes of aortic aneurysm were analyzed in each group. The inflammation, adhesion moleculesexpression, and PSGL-1 mediated leukocyte–endothelial adhesion and their underlying mechanisms were explored further.Results Increased PSGL-1 levels were observed in human and mouse aortic aneurysm, and on leukocytes of mice treated withDOCA+HS. PSGL-1 deficiency reduced the incidence and severity of aortic aneurysm significantly, as well as decreased elastinfragmentation, collagen accumulation, and smooth muscle cells degeneration. Mechanistically, the protective effect of PSGL-1inhibition was mediated by the reduced adhesion molecules, and the subsequently reduced leukocyte–endothelial adhesionthrough the NF-κB pathway, which finally led to reduced inflammatory cells infiltration and decreased inflammatory factorsexpression.Conclusion PSGL-1 deficiency is protective against inflammatory cells migration and recruitment in the condition of AA throughattenuation of leukocyte–endothelial adhesion. Inhibition of PSGL-1 may be a potential therapeutic target for the prevention andtreatment of human AA.Keywords Aortic aneurysm . PSGL-1 . Inflammation . Leukocyte–endothelial adhesion