Affordable Access

deepdyve-link
Publisher Website

Silencing of junctional adhesion molecule-like protein attenuates atherogenesis and enhances plaque stability in ApoE-/- mice.

Authors
  • Sun, Yu1, 2
  • Guan, Juan1
  • Hou, Yunfeng3
  • Xue, Fei2
  • Huang, Wei1
  • Zhang, Wencheng2
  • Zhang, Yun2
  • Zhang, Cheng2
  • Yang, Jianmin4
  • 1 The Shandong Provincial Key Laboratory of Infection and Immunology, Department of Pharmacology, School of Basic Medical Science, Shandong University, Jinan, Shandong, China. , (China)
  • 2 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China. , (China)
  • 3 Intensive Care Unit, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China. , (China)
  • 4 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China [email protected] , (China)
Type
Published Article
Journal
Clinical Science
Publisher
Portland Press
Publication Date
Jun 14, 2019
Volume
133
Issue
11
Pages
1215–1228
Identifiers
DOI: 10.1042/CS20180561
PMID: 31101724
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Background: Although junctional adhesion molecule-like protein (JAML) has recently been implicated in leukocyte recruitment during inflammation and wound repair, its role in atherosclerosis remains to be elucidated. Methods and results: First, we showed that JAML was strongly expressed in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with atherosclerotic plaques of ApoE-/- mice. Co-immunofluorescence staining showed that JAML was mainly expressed in macrophages. Enhanced expression of JAML in cultured macrophages was observed following exposure of the cells to oxLDL. The functional role of JAML in atherosclerosis and macrophages function was assessed by interference of JAML with shRNA in vivo and siRNA in vitro Silencing of JAML in mice significantly attenuated atherosclerotic lesion formation, reduced necrotic core area, increased plaque fibrous cap thickness, decreased macrophages content and inflammation. In addition, histological staining showed that JAML deficiency promoted plaques to stable phenotype. In vitro, JAML siRNA treatment lowered the expression of inflammatory cytokines in macrophages treated with oxLDL. The mechanism by which JAML mediated the inflammatory responses may be related to the ERK/NF-κB activation. Conclusions: Our results demonstrated that therapeutic drugs which antagonize the function of JAML may be a potentially effective approach to attenuate atherogenesis and enhance plaque stability. © 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Report this publication

Statistics

Seen <100 times