The Essential Role of Pin1 via NF-κB Signaling in Vascular Inflammation and Atherosclerosis in ApoE-/- Mice.

Abstract

Atherosclerosis, as a chronic inflammatory disease, is the major underlying cause of death worldwide. However, the mechanisms that underlie the inflammatory process are not completely understood. Prolyl-isomerase-1 (Pin1), as a unique peptidyl-prolyl isomerase, plays an important role in inflammation and endothelial dysfunction. Herein, we investigate whether Pin1 regulates vascular inflammation and atherosclerosis, and clarify its mechanisms in these processes. ApoE-/- mice were randomly given either juglone (0.3, 1 mg/kg, two times per week) or vehicle i.p. for 4 weeks. Compared with ApoE-/- mice, treatment by juglone resulted not only in markedly attenuated macrophage infiltration and atherosclerotic lesion area in a lipid-independent manner, but also in decreased expression of Pin1, vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), and NF-κB activity in aorta. Then, EA.hy926 cells were pretreated with juglone (6 μmol/L), Pin1 siRNA, NF-κB inhibitor, or vehicle prior to exposure to ox-LDL (50 μg/mL). It was observed that treatment with juglone or Pin1 siRNA suppressed expression of VCAM-1 in oxLDL-incubated EA.hy926 cells and decreased THP-1 cell adhesion to oxLDL-stimulated endothelial cells through the NF-κB signal pathway. Our findings indicate that Pin1 plays a vital role on the development of vascular inflammation and atherosclerosis.

• Authors: Ming Liu, Peng Yu, Hong Jiang, Xue Yang, Ji Zhao, Yunzeng Zou, Junbo Ge
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 3 (Mar 16 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28300760 (Publication Type: Journal Article)

Chemical References

• Apolipoproteins E
• Chemokine CCL2
• NF-kappa B
• NIMA-Interacting Peptidylprolyl Isomerase
• Naphthoquinones
• Vascular Cell Adhesion Molecule-1
• juglone

Topics

• Animals
• Aorta (metabolism, pathology)
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (metabolism)
• Cell Line
• Chemokine CCL2 (genetics, metabolism)
• Endothelium, Vascular (drug effects, metabolism)
• Humans
• Macrophages (drug effects)
• Male
• Mice
• NF-kappa B (genetics, metabolism)
• NIMA-Interacting Peptidylprolyl Isomerase (genetics, metabolism)
• Naphthoquinones (pharmacology)
• Signal Transduction
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)