P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt
P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt
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DOI：
10.1007/s10557-020-07135-1
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发表时间：
2021-01
影响因子：
3.4
通讯作者：
Xian-xian Wu;Xing Liu;Hang Yang;Qianlong Chen;N. Zhang;Yuhan Li;Xingchen Du;Xue Liu;Xiaoliang Jiang;Yideng Jiang;Zhou Zhou-Zhou;Zhiwei Yang
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作者：
Xian-xian Wu;Xing Liu;Hang Yang;Qianlong Chen;N. Zhang;Yuhan Li;Xingchen Du;Xue Liu;Xiaoliang Jiang;Yideng Jiang;Zhou Zhou-Zhou;Zhiwei Yang
目的P-选择素糖蛋白配体-1（PSGL-1）通过介导白细胞粘附，在炎症细胞浸润中起重要调节作用。然而，PSGL-1在主动脉瘤中的作用仍然难以捉摸。在这里，我们调查PSGL-1在主动脉瘤（AA）development.MethodsWe的作用，首先检测PSGL-1的表达，从主动脉瘤患者和小鼠AA模型通过Western印迹，免疫荧光，流式细胞仪，然后我们使用全球PSGL-1基因敲除小鼠和野生型对照建立一个主动脉瘤模型由醋酸脱氧皮质酮（DOCA）加高盐（HS）。分析各组主动脉瘤的发生率、病死率和病理变化。炎症，粘附分子的表达，和PSGL-1介导的白细胞内皮细胞粘附和其潜在的mechanisms explored further. ResultsPSGL-1水平增加，观察到在人类和小鼠的主动脉瘤，和白细胞DOCA+HS治疗的小鼠。PSGL-1缺乏可显著降低主动脉瘤的发生率和严重程度，并减少弹性蛋白断裂、胶原积聚和平滑肌细胞变性。结论PSGL-1抑制剂通过减少粘附分子的表达，进而通过NF-κB B途径减少白细胞与内皮细胞的粘附，最终减少炎症细胞浸润，降低炎症因子的表达，从而抑制AA时炎症细胞的迁移和募集。抑制PSGL-1可能是预防和治疗人类AA的潜在治疗靶点。
PurposeP-selectin glycoprotein ligand-1 (PSGL-1) acts as a crucial regulator for the inflammatory cells infiltration by mediating the adhesion of leukocytes. However, the role of PSGL-1 in aortic aneurysm remains elusive. Here, we investigated the role of PSGL-1 in aortic aneurysm (AA) development.MethodsWe first detected PSGL-1 expression in samples from aortic aneurysm patients and mouse AA models via western blotting, immunofluorescence, and flow cytometry, and then we used global PSGL-1 knockout mice and their wild type controls to establish an aortic aneurysm model induced by deoxycorticosterone acetate (DOCA) plus high salt (HS). The incidence, fatality rates, and the pathological changes of aortic aneurysm were analyzed in each group. The inflammation, adhesion molecules expression, and PSGL-1 mediated leukocyte–endothelial adhesion and their underlying mechanisms were explored further.ResultsIncreased PSGL-1 levels were observed in human and mouse aortic aneurysm, and on leukocytes of mice treated with DOCA+HS. PSGL-1 deficiency reduced the incidence and severity of aortic aneurysm significantly, as well as decreased elastin fragmentation, collagen accumulation, and smooth muscle cells degeneration. Mechanistically, the protective effect of PSGL-1 inhibition was mediated by the reduced adhesion molecules, and the subsequently reduced leukocyte–endothelial adhesion through the NF-κB pathway, which finally led to reduced inflammatory cells infiltration and decreased inflammatory factors expression.ConclusionPSGL-1 deficiency is protective against inflammatory cells migration and recruitment in the condition of AA through attenuation of leukocyte–endothelial adhesion. Inhibition of PSGL-1 may be a potential therapeutic target for the prevention and treatment of human AA.