Endothelial dysfunction induced by antibodies against angiotensin AT1 receptor in immunized rats.
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.
Zhang
Su-li
SL
Department of Physiology, Shanxi Medical University, Taiyuan, China.
Du
Yun-hui
YH
Wang
Jin
J
Yang
Li-hong
LH
Yang
Xiao-li
XL
Zheng
Rong-hua
RH
Wu
Ye
Y
Wang
Ke
K
Zhang
Ming-sheng
MS
Liu
Hui-rong
HR
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
D001323:Autoantibodies; D019332:Endothelin-1; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; D018799:Intercellular Adhesion Molecule-1; D007770:L-Lactate Dehydrogenase