PMID- 25041990
OWN - NLM
STAT- MEDLINE
DCOM- 20160504
LR  - 20151124
IS  - 1097-6809 (Electronic)
IS  - 0741-5214 (Linking)
VI  - 62
IP  - 6
DP  - 2015 Dec
TI  - Attenuation of early atherosclerotic lesions by immunotolerance with beta2 
      glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a 
      murine model.
PG  - 1625-31
LID - S0741-5214(14)01122-7 [pii]
LID - 10.1016/j.jvs.2014.05.096 [doi]
AB  - OBJECTIVE: This study assessed the effect of cellular and humoral autoimmune 
      response inhibition after immunization with beta2-glycoprotein I (beta2-GPI) and the 
      effect of immunomodulation with interleukin (IL)-2 and IL-10 in the development 
      of early atherosclerotic vascular lesion in a murine model. Atherosclerosis is 
      increasingly considered a chronic inflammatory disease with pathogenic autoimmune 
      processes. Regulatory T cells, and their cytokines, have been implicated in the 
      inhibition of the development of atherosclerotic lesions and involved in the 
      immunologic tolerance induction. METHODS: Eight-week-old male C57BL6 LDL-receptor 
      deficient (LDLR(-/-)) mice were fed a cholesterol-rich (2.8%), high-saturated-fat 
      (82%) diet for a week and divided in five groups. The groups received the 
      following intravenous immunizations: group I (control group): one dose of 5 mug 
      beta2-GPI; group II: 5 mug beta2-GPI I and 1 mug IL-2; group III: 5 mug beta2-GPI and 0.75 mug 
      of IL-10; and group IV: 5 mug beta2-GPI, 1 mug IL-2, and 0.75 mug IL-10. The aortas of 
      the mice were assessed 8 weeks after inoculation to determine the aortic lesion 
      size and composition in all groups. RESULTS: beta2-GPI immunization attenuated the 
      early atherosclerotic lesions development compared with the control group (P = 
      .001). Macroscopic and histologic aortic atherosclerotic lesions were 
      significantly decreased in the IL-2 and IL-10-treated groups in beta2-GPI-tolerant 
      mice compared with the beta2-GPI-tolerant group without cytokine injection (P = 
      .001). The association of both cytokines did not provoke a major inhibition in 
      the atherosclerosis development when compared with groups injected with the two 
      cytokines separately. CONCLUSIONS: The immunotolerance induction against beta2-GPI 
      attenuates the development of atherosclerosis lesions in an animal model, 
      enhanced by downregulation of the cellular and humoral autoimmune response 
      provoked by IL-2 and IL-10.
CI  - Copyright (c) 2015 Society for Vascular Surgery. Published by Elsevier Inc. All 
      rights reserved.
FAU - De Haro, Joaquin
AU  - De Haro J
AD  - Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, 
      Madrid, Spain. Electronic address: deharojoaquin@yahoo.es.
FAU - Esparza, Leticia
AU  - Esparza L
AD  - Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, 
      Madrid, Spain.
FAU - Bleda, Silvia
AU  - Bleda S
AD  - Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, 
      Madrid, Spain.
FAU - Varela, Cesar
AU  - Varela C
AD  - Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, 
      Madrid, Spain.
FAU - Sanchez, Carolina
AU  - Sanchez C
AD  - Biomedical Research Centre, Getafe University Hospital, Getafe, Madrid, Spain.
FAU - Acin, Francisco
AU  - Acin F
AD  - Angiology and Vascular Surgery Department, Getafe University Hospital, Getafe, 
      Madrid, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140717
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Interleukin-2)
RN  - 0 (beta 2-Glycoprotein I)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Aortic Diseases/*immunology/*pathology/physiopathology
MH  - Atherosclerosis/*immunology/*pathology/physiopathology
MH  - Disease Models, Animal
MH  - Down-Regulation/immunology
MH  - Humans
MH  - Immune Tolerance/drug effects/*physiology
MH  - Immunity, Cellular
MH  - Immunomodulation/*drug effects/physiology
MH  - Interleukin-10/*pharmacology/physiology
MH  - Interleukin-2/*pharmacology/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - beta 2-Glycoprotein I/*physiology
EDAT- 2014/07/22 06:00
MHDA- 2016/05/05 06:00
CRDT- 2014/07/22 06:00
PHST- 2014/02/04 00:00 [received]
PHST- 2014/05/24 00:00 [accepted]
PHST- 2014/07/22 06:00 [entrez]
PHST- 2014/07/22 06:00 [pubmed]
PHST- 2016/05/05 06:00 [medline]
AID - S0741-5214(14)01122-7 [pii]
AID - 10.1016/j.jvs.2014.05.096 [doi]
PST - ppublish
SO  - J Vasc Surg. 2015 Dec;62(6):1625-31. doi: 10.1016/j.jvs.2014.05.096. Epub 2014 
      Jul 17.