P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt.

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.

• Authors: Xianxian Wu, Xing Liu, Hang Yang, Qianlong Chen, Na Zhang, Yuhan Li, Xingchen Du, Xue Liu, Xiaoliang Jiang, Yideng Jiang, Zhou Zhou, Zhiwei Yang
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 36 Issue 1 Pg. 31-44 (02 2022) ISSN: 1573-7241 [Electronic] United States
• PMID: 33432452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Membrane Glycoproteins
• P-selectin ligand protein
• Sodium Chloride, Dietary
• Desoxycorticosterone Acetate

Topics

• Animals
• Aortic Aneurysm (genetics, physiopathology)
• Cell Adhesion (physiology)
• Cell Movement (physiology)
• Cells, Cultured
• Desoxycorticosterone Acetate
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Humans
• Inflammation (genetics, physiopathology)
• Leukocytes (metabolism)
• Male
• Membrane Glycoproteins (genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Patient Acuity
• Sodium Chloride, Dietary