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Comparison of the effects on maternal endothelial cell activation: an in vitro study of anti-hypertensive drugs clinically used in pre-eclampsia

Journal of Human Hypertension volume 36, pages 192–200 (2022)Cite this article

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Abstract

Endothelial cell dysfunction in pregnancy, which can be induced by placental factors, is the fundamental component of the pathogenesis of pre-eclampsia. The dysfunctional vascular endothelium disrupts the balance of vasodilatory and vasoconstrictive factors, resulting in increasing blood pressure. There is currently no effective treatment for pre-eclampsia and effective control of hypertension may reduce neonatal morbidity and mortality by prolonging gestation, especially in cases of early onset disease. To date methyldopa, labetalol, nifedipine and metoprolol are recommended for controlling blood pressure in pre-eclampsia. All of these drugs have different mechanisms of action. In this in vitro study we investigated whether different types of anti-hypertensive drugs could have different effects on improving maternal endothelial cell dysfunction. Endothelial cells (HMEC-1) were exposed to phorbol-12-myristate-13-acetate (PMA) or pre-eclamptic sera or extracellular vesicles (EVs) derived from pre-eclamptic placentae, in the presence of each of the studied anti-hypertensive drugs (methyldopa, labetalol, nifedipine and metoprolol) or placebo for 24 h. Endothelial cell-surface adhesion molecule (ICAM-1) and monocyte adhesion were measured. The expression of cell-face ICAM-1 by HMEC-1 cells and THP-1 monocyte adherent to HMEC-1 that were exposed to three separate well-known activators of endothelial cells in the presence of four anti-hypertensive drugs was significantly reduced regardless of the dose. However, the effect on the reduction of ICAM-1 expression and monocyte adhesion was not significantly different between the four medications. Our data suggest that the beneficial effect on improving endothelial cell function by these commonly prescribed anti-hypertensive drugs is seemingly independent of the anti-hypertensive mechanisms of the medication.

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Fig. 1: Anti-hypertensive drugs did not induce endothelial cell death.
Fig. 2: The effect on prevetion of endothelial cell activation induced by PMA was not different btween anti-hypertensive drugs.
Fig. 3: The effect on prevetion of endothelial cell activation induced by preeclamptic sera was not different btween anti-hypertensive drugs.
Fig. 4: The effect on prevetion of endothelial cell activation induced by placental EVs was not different btween anti-hypertensive drugs.

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Acknowledgements

We would like to thank women with pre-eclampsia who donated blood samples and placentae.

Funding

This study was supported by a School of Medicine Performance based research fund (PBRF) funding from The University of Auckland, New Zealand and A+  trust from Auckland City Hospital, New Zealand.

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Author notes

  1. These authors equally contributed: Esther Woolston, Yunhui Tang.

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand

    Esther Woolston, Larry Chamley, Peter Stone & Qi Chen

  2. The Hospital of Obstetrics and Gynaecology, Fudan University, Shanghai, China

    Yunhui Tang & Qi Chen

  3. National Women’s Health, Auckland City Hospital, Auckland, New Zealand

    Yunhui Tang, Sonia Azizi & Ian Kando

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  1. Esther Woolston
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Correspondence to Yunhui Tang.

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Woolston, E., Tang, Y., Azizi, S. et al. Comparison of the effects on maternal endothelial cell activation: an in vitro study of anti-hypertensive drugs clinically used in pre-eclampsia. J Hum Hypertens 36, 192–200 (2022). https://doi.org/10.1038/s41371-021-00497-5

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