Department of Physiology, Shanxi Medical University, Taiyuan, China.
Acta Pharmacol Sin. 2010 Oct;31(10):1381-8. doi: 10.1038/aps.2010.144. Epub 2010 Sep 13.
To investigate the association between autoantibodies against angiotensin AT1 receptor (AT1-AAs) and endothelial dysfunction in vivo.
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.
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.
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.
探讨血管紧张素 AT1 受体自身抗体（AT1-Abs）与体内内皮功能障碍的关系。
通过主动免疫九个月建立 AT1 受体抗体（AT1-Abs）大鼠模型。将乳酸脱氢酶（LDH）活性作为细胞坏死死亡的指标。测定大鼠血清中内皮素-1（ET-1）的含量，并检测分离的胸主动脉内皮依赖性血管舒张功能。使用共聚焦显微镜评估主动脉内皮细胞中细胞间黏附分子-1（ICAM-1）的表达。观察冠状动脉内皮超微结构。
与对照组 IgG 相比，免疫组 IgG 可通过 AT1 受体显著增加孵育的人脐静脉内皮细胞的 LDH 活性（0.84±0.17 对 0.39±0.12，P<0.01）。免疫组大鼠的 ET-1 含量高于对照组，分别在第 3 个月（27±4 ng/L，P<0.01）和第 7 个月（35±5 ng/L，P<0.01）达到两个峰值。此外，主动脉内皮依赖性血管舒张功能减弱；免疫后主动脉内皮 ICAM-1 水平显著升高，心肌毛细血管内皮受损。
本研究表明，AT1-Abs 导致体内内皮功能障碍，这可能是抗体在相关疾病中发挥重要作用的潜在机制。
