title: Endothelial dysfunction induced by antibodies against angiotensin AT1 receptor in immunized rats.
abstract: OBJECTIVE
  To investigate the association between autoantibodies against angiotensin AT1 receptor (AT1-AAs) and endothelial dysfunction in vivo.
  
  
  METHODS
  Rat models with AT1 receptor antibodies (AT1-Abs) were established by active immunization for nine months. Lactate dehydrogenase (LDH) activity was regarded as an indicator of cell necrotic death. Endothelin-1 (ET-1) in the sera of rats was determined and endothelium-dependent vasodilatation was detected in isolated thoracic aorta. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression in aorta endothelium was assessed using confocal microscopy. Coronary artery endothelial ultrastructure was observed.
  
  
  RESULTS
  IgGs in the immunized group significantly increased the LDH activity (0.84±0.17 vs 0.39±0.12, P<0.01 vs vehicle group IgGs)in incubated human umbilical vein endothelial cells through AT1 receptor. Higher content of ET-1 occurred in the immunized rats than that of the vehicle group, and reached two peaks at month 3 (27±4 ng/L, P<0.01) and month 7 (35±5 ng/L, P<0.01), respectively. In addition, aortic endothelium-dependent vasodilatation was attenuated; endothelial ICAM-1 level was markedly increased and cardiac capillary endothelium was damaged following immunization.
  
  
  CONCLUSIONS
  Our study demonstrated that AT1-Abs contributed to endothelial dysfunction in vivo, which was a potential mechanism through which the antibodies play vital roles in related diseases.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, China.
authors.forename: Su-li
authors.initials: SL
authors.lastname: Zhang
authors.forename: Yun-hui
authors.initials: YH
authors.lastname: Du
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Yang
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Yang
authors.forename: Rong-hua
authors.initials: RH
authors.lastname: Zheng
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Ming-sheng
authors.initials: MS
authors.lastname: Zhang
authors.forename: Hui-rong
authors.initials: HR
authors.lastname: Liu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000503:physiopathology; D001323:Autoantibodies / Q000378:metabolism*; D002196:Capillaries / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004789:Enzyme Activation; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology* / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism; D014664:Vasodilation
chemical_list: D001323:Autoantibodies; D019332:Endothelin-1; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; D018799:Intercellular Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase