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Int. J. Mol. Sci. 2017, 18(3), 644;

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

Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Michael Henein
Received: 21 February 2017 / Revised: 10 March 2017 / Accepted: 13 March 2017 / Published: 16 March 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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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. View Full-Text
Keywords: Pin1; NF-κB; inflammation; atherosclerosis Pin1; NF-κB; inflammation; atherosclerosis

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Liu, M.; Yu, P.; Jiang, H.; Yang, X.; Zhao, J.; Zou, Y.; Ge, J. The Essential Role of Pin1 via NF-κB Signaling in Vascular Inflammation and Atherosclerosis in ApoE−/− Mice. Int. J. Mol. Sci. 2017, 18, 644.

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