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

Abstract

BackgroundWomen with normotensive pregnancy are at a reduced risk of developing cardiovascular disease postpartum compared to 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 risk of cardiovascular disease following normotensive pregnancy. ObjectiveThis 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 DesignSpontaneously hypertensive rats were injected with placental EVs 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 remodelling, small artery remodelling, and renal function were investigated to comprehensively assess the impact of placental extracellular vesicles on cardiovascular and renal health. ResultsCompared to 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 to the control. Moreover, treatment with placental extracellular vesicles reduced wall thickening of small renal vessels and attenuated renal fibrosis. ConclusionPlacental extracellular vesicles from normotensive term pregnancies have long-lasting protective effects reducing hypertension and mitigating cardiovascular damage in vivo.