Abstract
Aim:
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.
Conclusion:
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.
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Acknowledgements
This research is supported in part by grants from Key Laboratory of Medical Electrophysiological Open Foundation of Sichuan Province to Su-li ZHANG, Basic Research Project of Shanxi Province (2008011076-2) to Li-hong YANG, and NSFC (National Natural Science Foundation of China, 30900584) to Xiao-li YANG.
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Zhang, Sl., Du, Yh., Wang, J. et al. Endothelial dysfunction induced by antibodies against angiotensin AT1 receptor in immunized rats. Acta Pharmacol Sin 31, 1381–1388 (2010). https://doi.org/10.1038/aps.2010.144
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DOI: https://doi.org/10.1038/aps.2010.144
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