Endothelial dysfunction and vascular stiffness in women with previous pregnancy complicated by early or late pre‐eclampsia

Orabona, Rossana; Sciatti, Edoardo; Vizzardi, Enrico; Bonadei, Ivano; Valcamonico, Adriana; Metra, Marco; Frusca, T.

doi:10.1002/uog.15893

Cited by 61 publications

(52 citation statements)

References 56 publications

(67 reference statements)

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“…One emerging hypothesis for this association is irreversible endothelial damage sustained during the preeclamptic pregnancy. In support of this hypothesis, healthy women with a history of preeclamptic pregnancy demonstrate increased arterial stiffness 11–14 and attenuated brachial artery flow-mediated dilation 11, 15 compared to women with a history of normal pregnancy. However, despite this compelling evidence for lasting endothelial damage in formerly preeclamptic women, few, if any, in vivo human studies investigated the mechanism(s) responsible for this persistent vessel dysfunction in postpartum women.…”

Section: Introductionmentioning

confidence: 84%

“…These studies speak solely to the first year post-delivery, and it remains unclear if endothelial function may recover in these women over time. Vascular studies of conduit vessel endothelial function and arterial stiffness suggest that vascular impairments are detectable in women who have had preeclampsia ≤4 years, and possibly even 20 years after delivery 14, 46–48 . As such, the vascular injury that occurs during a preeclamptic pregnancy likely persists throughout the patient’s life.…”

Section: Discussionmentioning

confidence: 99%

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Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia

et al. 2017

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Women who have had preeclampsia have increased CVD risk, however the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist post-partum. The putative mechanisms mediating this dysfunction include a reduction in nitric oxide (NO)-dependent dilation, and an increased sensitivity to angiotensin II (ang II). In this study, we evaluated endothelium-dependent dilation, ang II sensitivity, and the therapeutic effect of ang II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (PrEC, n=12) and control women who had a healthy pregnancy (HC, n=12). We hypothesized that PrEC would have 1) reduced endothelium-dependent dilation, 2) reduced NO-mediated dilation, and 3) increased sensitivity to ang II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in PrEC. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (ACh; 10−7–102mmol/L) and a standardized local heating protocol in control sites and sites treated with 15mmol/L L-NAME (NO-synthase inhibitor) or 43μmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to ang II (10−20–10−4mol/L). PrEC had significantly reduced endothelium-dependent dilation (−0.3±0.5 vs −1.0±0.4 logEC50; P<0.001) and NO-dependent dilation (16±3 vs 39±6%; P=0.006). PrEC also had augmented vasoconstrictor sensitivity to ang II (−10.2±1.3 vs −8.3±0.5; P=0.006). AT1R-inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in PrEC but had no effect in HC. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction post-partum, mediated in part by increased sensitivity to ang II.

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Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia

et al. 2017

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“…However, our smaller sample size precluded sub-analysis to explore the effect of time-since-delivery on our microvascular outcomes, and it remains unclear if microvascular function may recover in these women over time. Vascular studies of conduit vessel endothelial function and arterial stiffness suggest that vascular impairments are detectable in women who have had preeclampsia ≤4 years, and possibly even 20 years after delivery(16, 59-61). As such, the vascular injury that occurs during a preeclamptic pregnancy likely persists throughout the patient’s life.…”

Section: Discussionmentioning

confidence: 99%

“…hypertension, proteinuria, edema). In support of this hypothesis, otherwise healthy women with a history of preeclampsia demonstrate increased arterial stiffness (13-16), attenuated brachial artery flow-mediated dilation(13, 17), increased retrograde shear rate(18), increased coronary artery calcification(19), and augmented vasoconstrictor responses(20, 21) compared to women with a history of normal pregnancy. However, few in vivo human studies have examined the specific mechanistic underpinnings of this dysfunction.…”

Section: Introductionmentioning

confidence: 88%

Alterations in endothelin type B receptor contribute to microvascular dysfunction in women who have had preeclampsia

et al. 2017

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Microvascular dysfunction originating during a preeclamptic pregnancy persists postpartum and likely contributes to increased CVD risk in these women. One putative mechanism contributing to this dysfunction is increased vasoconstrictor sensitivity to endothelin-1 (ET-1), mediated by alterations in ET-1 receptor type-B (ETBR). We evaluated ET-1 sensitivity, ETAR and ETBR contributions to ET-1-mediated constriction, and the mechanistic role of ETBR in endothelium-dependent dilation in vivo in the microvasculature of postpartum women who had preeclampsia (PrEC, n=12) and control women who had a healthy pregnancy (HC, n=12). We hypothesized that 1) PrEC would have a greater vasoconstrictor response to ET-1, and 2) reduced ETBR-mediated dilation. We further hypothesized that ETBR-blockade would attenuate endothelium-dependent vasodilation in HC, but not PrEC. Microvascular reactivity was assessed by measurement of cutaneous vascular conductance responses to graded infusion of ET-1 (10-20-10-8mol/L), ET-1+500nmol/L BQ-123 (ETAR-blockade), and ET-1+300nmol/L BQ-788 (ETBR-blockade), and during graded infusion of acetylcholine (ACh, 10-7-102mmol/L) and a standardized local heating protocol with and without ETBR-inhibition. PrEC had an increased vasoconstriction response to ET-1 (P=0.02). PrEC demonstrated reduced dilation responses to selective ETBR stimulation with ET-1 (P=0.01). ETBR-inhibition augmented ET-1 mediated constriction in HC (P=0.01) but attenuated ET-1 mediated constriction in PrEC (P=0.003). ETBR-inhibition attenuated endothelium-dependent vasodilation responses to 100mmol/L ACh (P=0.04) and local heat (P=0.003) in HC but increased vasodilation (ACh: P= 0.01; local heat: P=0.03) in PrEC. Women who have had preeclampsia demonstrate augmented vasoconstrictor sensitivity to ET-1, mediated by altered ETBR signaling. Furthermore, altered ETBR function contributes to diminished endothelium-dependent dilation in previously preeclamptic women.

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“…Pre‐eclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, and its effects do not end with delivery: it is associated with a lifelong increased cardiovascular (CV) risk. This increased risk can be explained in part by left ventricular (LV) systodiastolic impairment, arterial stiffening and endothelial dysfunction, which have been documented both during and after PE. These phenomena, which influence each other, are related to myocardial and vascular remodeling, a process not yet fully understood which leads to loss of function and fibrous tissue deposition.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound evaluation of left ventricular and aortic fibrosis after pre‐eclampsia

Orabona

Sciatti

Vizzardi

et al. 2018

Ultrasound in Obstet & Gyne

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Endothelial dysfunction and vascular stiffness in women with previous pregnancy complicated by early or late pre‐eclampsia

Abstract: Objectives Pre-eclampsia (PE)

Cited by 61 publications

References 56 publications

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia

Alterations in endothelin type B receptor contribute to microvascular dysfunction in women who have had preeclampsia

Ultrasound evaluation of left ventricular and aortic fibrosis after pre‐eclampsia

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