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Autoantibodies Isolated from Preeclamptic Patients Induce Endothelial Dysfunction via Interaction with the Angiotensin II AT1 Receptor

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Abstract

Complete understanding of the etiology underlying endothelial damage in preeclampsia (PE) remains deficient. Recent studies suggest that autoantibodies against angiotensin II AT1 receptors (AT1-AA) may affect vascular endothelial integrity. However, direct evidence demonstrating association between AT1-AA from preeclamptic patients and vascular endothelial injury is lacking. The current study determined the effects of AT1-AA isolated from preeclamptic patients (Pre-IgG) upon the endothelium and attempted to elucidate the underlying mechanisms of injury. Pre-IgG markedly induced dose-dependent vasoconstriction in aortic vascular rings, an effect blocked by AT1 receptor antagonist losartan. Pre-IgG-induced vasoconstriction was increased in the absence of intact endothelium (1.59 ± 0.04 g vs. 1.63 ± 0.08 g, P < 0.05). Additionally, Pre-IgG incubation with human umbilical vein endothelial cells significantly increased lactate dehydrogenase release in a time-dependent manner (0.84 ± 0.07 vs. 3.50 ± 0.09, 24 vs. 72-h exposure group, P < 0.01) and increased caspase-3 and -8 activities (peaking at 48 h), but did not affect caspase-9 activity. Taken together, these results support the contribution of AT1-AA to endothelial cell injury and dysfunction in PE.

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Acknowledgments

This research is supported by the Natural Science Foundation of Shanxi Province of China (Grant No. 2013011050-5), the key scientific and technological projects of Shanxi Public Health Department (Grant No. 2011112), the Science and Technology Development Foundation of Taiyuan City (Grant No. 12016915), and the Shanxi Province science research project (Grant No. 20130313019-4).

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Authors and Affiliations

  1. Department of Reproductive Center, Taiyuan Central Hospital, Taiyuan, 030001, Shanxi, People’s Republic of China

    Xiaoli Yang & Shuo Zhang

  2. Department of Pathophysiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, People’s Republic of China

    Feng Wang

  3. Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, People’s Republic of China

    Feng Wang

  4. Department of Emergency Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Wayne Bond Lau & Xin-Liang Ma

  5. Department of Physiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, People’s Republic of China

    Suli Zhang & Huirong Liu

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  1. Xiaoli Yang
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Correspondence to Huirong Liu.

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Yang, X., Wang, F., Lau, W.B. et al. Autoantibodies Isolated from Preeclamptic Patients Induce Endothelial Dysfunction via Interaction with the Angiotensin II AT1 Receptor. Cardiovasc Toxicol 14, 21–29 (2014). https://doi.org/10.1007/s12012-013-9229-8

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