PMID- 24970589
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20211021
IS  - 1573-2592 (Electronic)
IS  - 0271-9142 (Linking)
VI  - 34
IP  - 6
DP  - 2014 Aug
TI  - Recombinant domain V of beta2-glycoprotein I inhibits the formation of atherogenic 
      oxLDL/beta2-glycoprotein I complexes.
PG  - 669-76
LID - 10.1007/s10875-014-0063-y [doi]
AB  - beta2-glycoprotein I (beta2-GPI) is a plasma protein that interacts with oxidized 
      low-density lipoproteins (oxLDL) via beta2-GPI domain V to form oxLDL/beta2-GPI 
      complexes, potential autoantigens promoting atherogenesis in patients with 
      antiphospholipid syndrome (APS). Such a interaction would expose beta2-GPI domain I 
      or/and IV, structures recognized by anti-beta2-GPI autoantibodies. IgG immune 
      complexes with oxLDL/beta2-GPI complexes can interact with macrophages via Fcgamma 
      receptor, causing oxLDL/beta2-GPI endocytosis and foam cell formation, contributing 
      to atherosclerosis. Here, we use recombinant domain V to study the interaction 
      between oxLDL and beta2-GPI and hypothesized that domain V would interfere with this 
      interaction thereby reducing oxLDL macrophage uptake and foam cell formation. The 
      beta2-GPI domain V sequence was expressed by using the Pichia pastoris expression 
      system to obtain recombinant domain V of beta2-GPI (P.rbeta2-GPI DV). ELISA tests 
      demonstrated that P.rbeta2-GPI DV interacted with oxLDL via 
      7-ketocholesteryl-9-carboxynonanoate (oxLig-1), a negatively charged lipid moiety 
      of oxLDL. The omega-carboxyl residue of oxLig-1 is required for the interaction. 
      Serologic tests showed a significant increase in oxLDL and oxLDL/beta2-GPI levels in 
      patients with APS (p < 0.05 compared to controls). P.rbeta2-GPI DV was able to bind 
      oxLDL in high affinity and competitively inhibited native beta2-GPI (nbeta2-GPI) 
      binding to free oxLDL as well as to oxLDL from the oxLDL/beta2-GPI complexes. These 
      observations suggest that P.rbeta2-GPI DV may be used to inhibit the formation of 
      the oxLDL/beta2-GPI complexes, a potential approach for reducing foam cell 
      development and mitigating atherogenesis in patients with APS. The present work 
      provides a new effective strategy to prevent the progression of atherothrombotic 
      vascular complications in APS patients.
FAU - Li, Jingda
AU  - Li J
AD  - Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life 
      Science and Technology, Dalian University, 10-Xuefu Avenue, Dalian Economical and 
      Technological Development Zone, Dalian, Liaoning, 116622, China.
FAU - Chi, Yan
AU  - Chi Y
FAU - Liu, Shuqian
AU  - Liu S
FAU - Wang, Le
AU  - Wang L
FAU - Wang, Renjun
AU  - Wang R
FAU - Han, Xiaofei
AU  - Han X
FAU - Matsuura, Eiji
AU  - Matsuura E
FAU - Liu, Qingping
AU  - Liu Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140627
PL  - Netherlands
TA  - J Clin Immunol
JT  - Journal of clinical immunology
JID - 8102137
RN  - 0 (7-ketocholesteryl-9-carboxynonanoate)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Cholesterol Esters)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Recombinant Proteins)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 0 (oxidized low density lipoprotein)
SB  - IM
MH  - Antigen-Antibody Complex/immunology/*metabolism
MH  - Antiphospholipid Syndrome/complications/*drug therapy
MH  - Atherosclerosis
MH  - Autoantibodies/immunology/metabolism
MH  - Autoantigens/immunology/*metabolism
MH  - Cholesterol Esters/metabolism
MH  - Endocytosis
MH  - Foam Cells/*physiology
MH  - Humans
MH  - Lipoproteins, LDL/*metabolism
MH  - Plaque, Atherosclerotic/etiology/*prevention & control
MH  - Protein Binding
MH  - Protein Structure, Tertiary/genetics
MH  - Recombinant Proteins/genetics
MH  - beta 2-Glycoprotein I/genetics/*metabolism
EDAT- 2014/06/28 06:00
MHDA- 2015/11/18 06:00
CRDT- 2014/06/28 06:00
PHST- 2013/04/19 00:00 [received]
PHST- 2014/05/20 00:00 [accepted]
PHST- 2014/06/28 06:00 [entrez]
PHST- 2014/06/28 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
AID - 10.1007/s10875-014-0063-y [doi]
PST - ppublish
SO  - J Clin Immunol. 2014 Aug;34(6):669-76. doi: 10.1007/s10875-014-0063-y. Epub 2014 
      Jun 27.