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Normotensive placental extracellular vesicles provide long-term protection against hypertension and cardiovascular disease - 24/01/24

Doi : 10.1016/j.ajog.2023.12.030 
Yourong Feng, MD a, , Sandy Lau, PhD a, Qi Chen, PhD, MD a, Charlotte Oyston, PhD a, Katie Groom, PhD b, Carolyn J. Barrett, PhD c, Lawrence W. Chamley, PhD a
a Department of Obstetrics and Gynaecology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand 
b Liggins Institute, The University of Auckland, Auckland, New Zealand 
c Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand 

Corresponding author: Yourong Feng, MD.
Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 24 January 2024

Abstract

Background

Women with normotensive pregnancy are at a reduced risk of developing cardiovascular disease postpartum compared with those who experience hypertensive conditions during pregnancy. However, the underlying mechanisms remain poorly understood. During normotensive pregnancy, vast numbers of placental extracellular vesicles are released into the maternal circulation, which protect endothelial cells from activation and alter maternal vascular tone. We hypothesized that placental extracellular vesicles play a mechanistic role in lowering the risk of cardiovascular disease following normotensive pregnancy.

Objective

This study aimed to investigate the long-term effects of placental extracellular vesicles derived from normotensive term placentae on the cardiovascular system and explore the mechanisms underlying their biological effects.

Study Design

Spontaneously hypertensive rats were injected with placental extracellular vesicles from normotensive term pregnancies (2 mg/kg each time, n=8) or vehicle control (n=9) at 3 months of age. Blood pressure and cardiac function were regularly monitored from 3 months to 15 months of age. The response of mesenteric resistance arteries to vasoactive substances was investigated to evaluate vascular function. Cardiac remodeling, small artery remodeling, and renal function were investigated to comprehensively assess the impact of placental extracellular vesicles on cardiovascular and renal health.

Results

Compared with vehicle-treated control animals, rats treated with normotensive placental extracellular vesicles exhibited a significantly lower increase in blood pressure and improved cardiac function. Furthermore, the vasodilator response to the endothelium-dependent agonist acetylcholine was significantly enhanced in the normotensive placental extracellular vesicle-treated spontaneously hypertensive rats compared with the control. Moreover, treatment with placental extracellular vesicles reduced wall thickening of small renal vessels and attenuated renal fibrosis.

Conclusion

Placental extracellular vesicles from normotensive term pregnancies have long-lasting protective effects reducing hypertension and mitigating cardiovascular damage in vivo.

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Key words : cardiovascular disease, normotensive pregnancy, placental extracellular vesicles, renal damage


Plan


 The authors report no conflict of interest.
 This work was funded by the Health Research Council of New Zealand (grant number HRC 21/209) and Y.F. was supported by a China Scholarship Council Scholarships.
 Cite this article as: Feng Y, Lau S, Chen Q, et al. Normotensive placental extracellular vesicles provide long-term protection against hypertension and cardiovascular disease. Am J Obstet Gynecol 2024;XX:x.ex–x.ex.


© 2023  The Author(s). Publié par Elsevier Masson SAS. Tous droits réservés.
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