Xianxian Wu1, Xing Liu1, Hang Yang2, Qianlong Chen2, Na Zhang3, Yuhan Li4, Xingchen Du4, Xue Liu1, Xiaoliang Jiang1, Yideng Jiang4, Zhou Zhou5, Zhiwei Yang6. 1. Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), 5 Pan Jia Yuan Nan Li Chaoyang District, Beijing, 100021, People's Republic of China. 2. State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Center of Laboratory Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. 3. Institute of Cardiovascular Diseases, General Hospital of Ningxia Medical University, Yinchuan, 750001, Ningxia, China. 4. School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China. 5. State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service, Center of Laboratory Medicine, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China. zhouzhou@fuwaihospital.org. 6. Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), 5 Pan Jia Yuan Nan Li Chaoyang District, Beijing, 100021, People's Republic of China. yangzhiwei@cnilas.pumc.edu.cn.
Abstract
PURPOSE: P-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. METHODS: We 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. RESULTS: Increased 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. CONCLUSION: PSGL-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.
PURPOSE: P-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. METHODS: We 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. RESULTS: Increased 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. CONCLUSION: PSGL-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.
Authors: Uwe Raaz; Alexander M Zöllner; Isabel N Schellinger; Ryuji Toh; Futoshi Nakagami; Moritz Brandt; Fabian C Emrich; Yosuke Kayama; Suzanne Eken; Matti Adam; Lars Maegdefessel; Thomas Hertel; Alicia Deng; Ann Jagger; Michael Buerke; Ronald L Dalman; Joshua M Spin; Ellen Kuhl; Philip S Tsao Journal: Circulation Date: 2015-04-22 Impact factor: 29.690
Authors: Daniel Y Li; Albert Busch; Hong Jin; Ekaterina Chernogubova; Jaroslav Pelisek; Joakim Karlsson; Bengt Sennblad; Shengliang Liu; Shen Lao; Patrick Hofmann; Alexandra Bäcklund; Suzanne M Eken; Joy Roy; Per Eriksson; Brian Dacken; Deepak Ramanujam; Anne Dueck; Stefan Engelhardt; Reinier A Boon; Hans-Henning Eckstein; Joshua M Spin; Philip S Tsao; Lars Maegdefessel Journal: Circulation Date: 2018-10-09 Impact factor: 29.690
Authors: N Patelis; D Moris; D Schizas; C Damaskos; D Perrea; C Bakoyiannis; T Liakakos; S Georgopoulos Journal: Physiol Res Date: 2017-09-22 Impact factor: 1.881