title: Pentraxin 3 promotes oxLDL uptake and inhibits cholesterol efflux from macrophage-derived foam cells.
abstract: BACKGROUND
  The objective of this study was to determine the effects of pentraxin3 (PTX3) on human oxidized low density lipoprotein (oxLDL) uptake and cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis.
  
  
  METHODS
  The effects of PTX3 on oxLDL uptake and cholesterol efflux were determined after transfection of human THP-1 macrophages with pSG5hPTX3 or PTX3siRNA plasmids. To evaluate the role of specific signaling pathways, human THP-1 cells were pre-treated with inhibitors of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), phosphatidylinositide 3-kinases (PI3-K), and p38 mitogen-activated protein kinase (MAPK) pathways (PD98059, LY294002, and SB203580, respectively), and then exposed to oxLDL for the uptake assay or oxLDL and [(3)H]-cholesterol and apolipoprotein A-I (apoA-I) for the cholesterol efflux assay.
  
  
  RESULTS
  PTX3 overexpression not only promoted oxLDL uptake but also significantly reduced cholesterol efflux to apoA-I; it also significantly decreased the expression of peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor alpha (LXRα) and ATP-binding membrane cassette transporter A-1 (ABCA1), which was increased with PTX3 silencing. Furthermore, PTX3 significantly increased p-ERK1/2 levels in THP-1-derived foam cells, and inhibition of ERK1/2 by PD98059 significantly reduced the oxLDL uptake and promoted the cholesterol efflux induced by PTX3 overexpression.
  
  
  CONCLUSIONS
  Here, we demonstrate that PTX3 affects lipid accumulation in human macrophages, increasing oxLDL uptake and inhibiting cholesterol efflux. That is the underlying possible mechanisms of PTX3 contribution to the progression of atherosclerosis.
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pathology of the First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Weishuo
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong Umversiy of Science and Technology, Wuhan, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yan
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dujuan
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yungui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Institute of Pathology of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: ruanqiurong@sina.com.
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Ruan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005487:Foam Cells / Q000378:metabolism*; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D000071518:Liver X Receptors; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D002097:C-Reactive Protein; D002784:Cholesterol; D002867:Chromones; D005419:Flavonoids; D007093:Imidazoles; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D048052:Mitogen-Activated Protein Kinase 3; D009025:Morpholines; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D011725:Pyridines; D000683:Serum Amyloid P-Component; D048051:p38 Mitogen-Activated Protein Kinases; D000099153:Pentraxins; C577836:ABCA1 protein, human; C000605213:NR1H3 protein, human; C099252:oxidized low density lipoprotein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Atherosclerosis; Macrophage; Pentraxin 3