title: ATRQβ-001 vaccine prevents atherosclerosis in apolipoprotein E-null mice.
abstract: OBJECTIVE
  Angiotensin II (AngII) type 1 receptor (AT1R) blockers have been proved to reduce atherosclerosis. Previously, we have invented ATRQβ-001 vaccine which showed a desirable blocking effect for AT1R. The purpose of this study was to investigate whether ATRQβ-001 vaccine would prevent atherosclerosis in apolipoprotein E-null (ApoE-/-) mice.
  
  
  METHODS
  Male ApoE-/- mice were administered with ATRQβ-001 vaccine, Qβ virus-like particles, valsartan or vehicle over a period of 24 weeks. In vitro, human coronary artery endothelial cells preincubated with the anti-ATR-001 antibody, the neutralization antibody or valsartan for 2  h, were treated with AngII for 24  h. Histological stain and molecule biology methods were used to assess the atheroprotective effect of the vaccine.
  
  
  RESULTS
  ATRQβ-001 vaccine significantly reduced the lesion area and promoted the stability of atherosclerotic plaque. Meanwhile, macrophage infiltration as well as the expressions of adhesion molecules and monocyte chemoattractant protein-1 was obviously decreased in the ATRQβ-001 vaccine group. Additionally, the vaccine markedly reduced the apoptosis in the lesions of the ApoE-/- mice. In vitro, the anti-ATR-001 antibody inhibited endothelial apoptosis induced by AngII. Furthermore, ATRQβ-001 vaccine exhibited a dramatical attenuation in the expressions of lectin-like oxidized low-density lipoprotein receptor-1 and AT1R in the aortic. More importantly, compared with the valsartan group, no obvious feedback of the plasma renin-angiotensin system was elicited in the vaccine group.
  
  
  CONCLUSIONS
  The results demonstrated that ATRQβ-001 vaccine reduced the progression of atherosclerosis in ApoE-/- mice without obvious feedback of renin-angiotensin system.
authors.affiliation: Laboratory of Cardiovascular Immunology, Key Laboratory of Molecular Targeted Therapies of the Ministry of Education, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China *Yanzhao Zhou, Shijia Wang and Zhihua Qiu contributed equally to the writing of this article. †Yuhua Liao and Xiao Chen contributed equally to this study.
authors.forename: Yanzhao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shijia
authors.initials: S
authors.lastname: Wang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Qiu
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Song
authors.forename: Yajie
authors.initials: Y
authors.lastname: Pan
authors.forename: Xiajun
authors.initials: X
authors.lastname: Hu
authors.forename: Hongrong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yihuan
authors.initials: Y
authors.lastname: Deng
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.forename: Hailang
authors.initials: H
authors.lastname: Wu
authors.forename: Shijun
authors.initials: S
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000187:drug effects / Q000276:immunology; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D012084:Renin-Angiotensin System; D051127:Scavenger Receptors, Class E / Q000187:drug effects / Q000378:metabolism; D014612:Vaccines / Q000494:pharmacology*; D000068756:Valsartan / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057134:Antibodies, Neutralizing; D001057:Apolipoproteins E; D018932:Chemokine CCL2; D044140:Receptor, Angiotensin, Type 1; D051127:Scavenger Receptors, Class E; D014612:Vaccines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000068756:Valsartan