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Long-term presence of angiotensin II type 1 receptor autoantibody reduces aldosterone production by triggering Ca2+ overload in H295R cells

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Abstract

Preeclamptic women are reported to have inadequate plasma volume expansion coupled with a suppressed secretion of aldosterone; however, the specific mechanism of preeclampsia remains unclear. We demonstrated that the presence of long-term angiotensin II type 1 receptor autoantibody (AT1-AA) reduces aldosterone production by triggering a Ca2+ overload in H295R cells. AT1-AA was discovered in preeclamptic women and reported to activate AT1R, and consequently elevate intracellular Ca2+. We found that AT1-AA significantly prolonged the time of intracellular Ca2+ elevation. Besides promoting aldosterone production as a second messenger, Ca2+ overload shows a cytotoxic effect. Our data reveals that long-term presence of AT1-AA triggered a Ca2+ overload and consequent impairment of aldosterone production, which could be prevented by a PKC inhibitor, Gö 6983, or a calcium channel inhibitor, nifedipine. These findings have clinical significance because AT1R blockers are not recommended for treatment of preeclampsia due to their potential harm to the fetus. Our findings also emphasize a potential clinical benefit of immunoadsorption or neutralization of AT1-AA in preeclamptic women.

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Funding

This work was supported by the grants from the Major Research plan of the National Natural Science Foundation of China (Grant No. 91539205) to Huirong Liu, the National Natural Science Foundation of China (Grant No.81471478) to Xiaoli Yang, and the Natural Science Foundation of Shanxi Province, China (Grant No.201601D011093) to Feng Wang.

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Authors and Affiliations

  1. Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, 10 Xitoutiao, You An Men Street, Beijing, 100069, China

    Jinghui Lei, Suli Zhang, Pengli Wang, Yang Liao, Jingwei Bian, Xiaochen Yin, Ye Wu, Lina Bai & Huirong Liu

  2. Beijing Key Laboratory of Cardiovascular Diseases and Related Metabolic Dysfunction, Capital Medical University, Beijing, China

    Jinghui Lei, Suli Zhang, Pengli Wang, Yang Liao, Jingwei Bian, Xiaochen Yin, Ye Wu, Lina Bai & Huirong Liu

  3. Department of Pathophysiology, Key Laboratory of Cell Physiology of Ministry of Education,The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China

    Feng Wang

  4. Department of Reproductive Center, Taiyuan Central Hospital, Taiyuan, Shanxi, 030009, China

    Xiaoli Yang

Authors
  1. Jinghui Lei
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  2. Suli Zhang
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  3. Pengli Wang
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  4. Yang Liao
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  5. Jingwei Bian
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  6. Xiaochen Yin
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  7. Ye Wu
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  8. Lina Bai
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  9. Feng Wang
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  10. Xiaoli Yang
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  11. Huirong Liu
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Corresponding authors

Correspondence to Xiaoli Yang or Huirong Liu.

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The protocol was approved by the Ethics Committee of Capital Medical University (Beijing, China).

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The authors declare that they have no conflict of interest.

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Lei, J., Zhang, S., Wang, P. et al. Long-term presence of angiotensin II type 1 receptor autoantibody reduces aldosterone production by triggering Ca2+ overload in H295R cells. Immunol Res 66, 44–51 (2018). https://doi.org/10.1007/s12026-017-8963-6

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  • DOI: https://doi.org/10.1007/s12026-017-8963-6

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