title: SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.
abstract: OBJECTIVE
  Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression.
  
  
  METHODS
  we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development.
  
  
  RESULTS
  SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages.
  
  
  CONCLUSIONS
  SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway.
authors.affiliation: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wu
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Dingwen
authors.initials: D
authors.lastname: Wen
authors.affiliation: Clinical Laboratory Department, The Second Hospital Affiliated to Guangzhou Medical University, PR China.
authors.forename: Tianxing
authors.initials: T
authors.lastname: Ji
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Xing
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: He
authors.affiliation: Vascular Biology Research Institute, School of Basic Courses, Guangzhou, 510006, PR China. Electronic address: wanglijing@gdpu.edu.cn.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D000683:Serum Amyloid P-Component / Q000172:deficiency* / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D000683:Serum Amyloid P-Component; D012313:RNA
keywords: Atherosclerosis; CD36; FcγRI; MAPK; Serum amyloid P component