title: PEDF improves atherosclerotic plaque stability by inhibiting macrophage inflammation response.
abstract: BACKGROUND
  Atherosclerosis is a vascular disease with plaque formation and growth. Instable plaque with chronic inflammation is closely related to adverse cardiac outcomes. Pigment epithelium-derived factor (PEDF) is an endogenous multifunctional cytokine that possesses the ability of anti-inflammation. The aim of this study is to detect whether PEDF has protective effect on the stability of atherosclerotic plaque and to explore whether the effect of anti-inflammation involved.
  
  
  RESULTS
  ApoE-/-mice fed with high fat diet and RAW264.7 cells were used to evaluate anti-inflammatory activities of PEDF both in vivo and in vitro. PEDF overexpression improved atherosclerotic plaque stability in ApoE-/-mice. The expression of inflammatory factors (interleukin-1β [IL-1β], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], monocyte chemotactic protein-1 [MCP-1] and matrix metalloproteinase [MMP-9]) was significantly decreased with PEDF overexpression in vivo and in vitro. The anti-inflammation effect of PEDF was attenuated by PPAR-γ specific antagonist GW9662. In addition, PEDF significantly decreased the expression of phosphorylated ERK-MAPK, p38-MAPK and JNK-MAPK. GW9662 partly reversed the PEDF-mediated depression of phosphorylated ERK- and p38-MAPK but has no significant effect on JNK-MAPK.
  
  
  CONCLUSIONS
  PEDF has protective effect on increasing AS plaque stability through ameliorating macrophage inflammation. PPAR-γ and downstream MAPKs were involved in the mechanism.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; Binzhou Medical University, Yantai, Shandong, China; Department of Cardiology, Dongying People's Hospital, Dongying, Shandong, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Ophthalmological Department, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ni
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Luan
authors.affiliation: Binzhou Medical University, Yantai, Shandong, China; Department of Cardiology, Dongying People's Hospital, Dongying, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Binzhou Medical University, Yantai, Shandong, China; Department of Cardiology, Dongying People's Hospital, Dongying, Shandong, China. Electronic address: xuxinshengdr@sohu.com.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China. Electronic address: lvhuixia2004@163.com.
authors.forename: Huixia
authors.initials: H
authors.lastname: Lu
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D001057:Apolipoproteins E / Q000276:immunology; D059305:Diet, High-Fat / Q000379:methods; D005136:Eye Proteins / Q000032:analysis / Q000276:immunology; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000032:analysis / Q000276:immunology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000503:physiopathology; D065840:Protective Factors; D015843:Serpins / Q000032:analysis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D000813:Anilides; D000893:Anti-Inflammatory Agents; D001057:Apolipoproteins E; D005136:Eye Proteins; D020928:Mitogen-Activated Protein Kinases; D009414:Nerve Growth Factors; D047495:PPAR gamma; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C457499:2-chloro-5-nitrobenzanilide
keywords: Atherosclerotic plaque stability; Inflammation; MAPK; PEDF; PPAR-γ