title: 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.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. lmingw0559@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. ypbaggio@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. jiang.hong@zs-hospital.sh.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. sherrina_1010@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. zhao.ji@zs-hospital.sh.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. zou.yunzeng@zs-hospital.sh.cn.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, 180 Fenglin Road, Shanghai 200032, China. jbge@zs-hospital.sh.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D018932:Chemokine CCL2; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones; D019010:Vascular Cell Adhesion Molecule-1; C005134:juglone
keywords: NF-κB; Pin1; atherosclerosis; inflammation