Evidence of impaired microvascular function in pre-eclampsia: a non-invasive study

ANIM-NYAME, N.; Gamble, J.; SOORANNA, S. R.; JOHNSON, M. R.; SULLIVAN, M. H.; STEER, P. J.

doi:10.1042/cs20020323

Cited by 17 publications

(19 citation statements)

References 22 publications

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“…ADAMTS13 Ag was measured in all samples and was undetectable in all cases. Finally, although not measured in our study, similar total protein concentrations in subjects with PE and normal pregnant controls have been reported, 45 which also argues against a role of increased vascular permeability in ADAMTS13 decrease.…”

Section: Discussionmentioning

confidence: 56%

Von Willebrand Factor and ADAMTS13

Stépanian

Cohen-Moatti²,

Sanglier³

et al. 2011

ATVB

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Objective-The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery). Methods and Results-We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin- Key Words: hypertension Ⅲ pregnancy Ⅲ ADAMTS13 Ⅲ preeclampsia Ⅲ von Willebrand factor P reeclampsia (PE) is the most frequent medical complication during pregnancy, occurring in Ϸ2% to 7% of pregnancies worldwide. 1,2 It is a major cause of perinatal and maternal mortality and morbidity. PE is characterized clinically by new onset hypertension and proteinuria after 20 weeks of gestation (WG). The pathogenesis of PE involves inadequate cytotrophoblast invasion with subsequent abnormal placentation, resulting in placental hypoperfusion and ischemia with microthrombotic lesions. 3,4 The ischemic placenta releases various molecules, including cytokines, antiangiogenic peptides, free reactive oxygen species that induce systemic maternal endothelial dysfunction, and excessive general inflammatory responses. 5,6 The pathophysiology of the placental microthrombosis observed in PE is obviously multifactorial and likely involves both the endothelium and plasma proteins. Among the various plasma proteins involved in thrombosis, the von Willebrand factor (VWF)/a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) couple is interesting to focus on, considering this specific hemorheologic context. VWF is a large multimeric plasma glycoprotein that notably mediates platelet adhesion and aggregation at high shear stress conditions thanks to its multimeric structure. 7 It is synthesized in endothelial cells and megakaryocytes and respectively stored in Weibel-Palade bodies and ␣ granules; VWF is formed in these compartments as ultralarge and very active VWF multimers. ADAMTS13 is a zinc metalloprotease that specifically cleaves the bond between amino acids Tyr1605 and Met1606 in the A2 domain of VWF exposed by shear stress. This protease activity reduces VWF molecular weight and consequently also its platelet-tethering function. 7,8 A severely deficient ADAMTS13 activity (less than 5% of

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Section: Discussionmentioning

confidence: 56%

Von Willebrand Factor and ADAMTS13

Stépanian

Cohen-Moatti²,

Sanglier³

et al. 2011

ATVB

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“…23,24 Although we did not specifically asses changes in vessel diameters and used different techniques in different organ systems, we did not observe major changes in large vessels, which mostly consist of venules and arterioles to a lesser extent. Hasan, using intravital capillaroscopy, reported a reduced capillary density in 11 women with pre-eclampsia, as compared with normal healthy pregnant and non-pregnant women.…”

Section: Interpretation and Relation To Other Studiesmentioning

confidence: 91%

Microcirculation in women with severe pre‐eclampsia and HELLP syndrome: a case–control study

Cornette

Herzog

Buijs

et al. 2013

BJOG

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Objective To compare microcirculatory perfusion in women with severe pre-eclampsia against that in healthy pregnant women, and secondly in women with severe pre-eclampsia with or without HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets).Design Case-control study.Setting University Hospital Rotterdam, the Netherlands.Population Twenty-three women with severe pre-eclampsia and 23 healthy pregnant controls, matched for maternal and gestational age. Out of the 23 women with severe pre-eclampsia, ten presented with HELLP syndrome.Methods Microcirculation was analysed sublingually by a non-invasive sidestream dark-field imaging device (SDF).Main outcome measures Perfused vessel density (PVD), microcirculatory flow index (MFI), and heterogeneity index (HI) were calculated for both small vessels (∅ < 20 lm; capillaries) and non-small vessels (∅ > 20 lm; venules and arterioles).Results There were no significant differences between women with severe pre-eclampsia and healthy controls. Women with pre-eclampsia and HELLP syndrome showed a reduced PVD (P = 0.045), MFI (P = 0.008), and increased HI (P = 0.002) for small vessels, as compared with women with pre-eclampsia but without HELLP syndrome.Conclusions Sidestream dark-field is a novel, promising technique in obstetrics that permits the non-invasive evaluation of microcirculation. We did not observe major differences in sublingual microcirculatory perfusion between women with severe pre-eclampsia and healthy pregnant controls. In women with severe pre-eclampsia, the presence of HELLP syndrome is characterised by impaired capillary perfusion.Keywords Capillary, HELLP syndrome, microcirculation, microcirculatory perfusion, pre-eclampsia, sidestream dark-field imaging.Please cite this paper as: Cornette J, Herzog E, Buijs EAB, Duvekot JJ, Rizopoulos D, Hop WCJ, Tibboel D, Steegers EAP. Microcirculation in women with severe pre-eclampsia and HELLP syndrome: a case-control study.

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“…Notably, however, there are no studies that we are aware of showing that endogenous sFlt (as opposed to mutated forms such as the VEGF-Traps [27]) inhibits VEGFmediated increased vascular permeability rather than fluid extravasation. Interestingly, a recent study [28] has shown that the 'isovolumetric venous pressure', equivalent in a whole organ to the balance of the effective σ π and the interstitial pressure, was significantly raised in pre-eclampsia. This effect was attributed to postcapillary margination of leucocytes resulting in increased fractional extraction of water and, therefore, increased π c at the microvascular interface.…”

Section: Figure 3 Correlation Between An Increase In L P With the Decmentioning

confidence: 97%

Plasma from women with severe pre-eclampsia increases microvascular permeability in an animal model in vivo

et al. 2004

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Pre-eclampsia results in oedema, hypertension and proteinuria, and is associated with increased vascular permeability. A number of studies have pointed to the existence of a circulating macromolecule that induces this endothelial dysfunction. To test whether this circulating factor could increase vascular permeability, we have measured the effect of dialysed human plasma from pregnant women with mild or severe pre-eclampsia (pre-eclamptic toxaemia). Plasma was collected from patients with mild or severe pre-eclampsia and from normotensive women. Plasma was dialysed against frog Ringer's solution using a 12-14 kDa molecular-mass cut-off dialysis tubing. pi c (colloid osmotic pressure) was measured with a modified Hansen oncometer. Lp (hydraulic conductivity) and sigma (oncotic reflection coefficient) were measured in individually perfused frog mesenteric microvessels using the Landis-Michel technique during perfusion with dialysed plasma. Perfusion of vessels with normal plasma or plasma from patients with mild pre-eclampsia did not alter either Lp or sigma. However, plasma from patients with severe pre-eclampsia resulted in a 3.8+/-0.3-fold increase in Lp and a reduction in sigma from 0.96+/-0.03 to 0.80+/-0.11. There was a significant correlation between the change in sigma and the change in Lp, suggesting that the increase in permeability was due to an increase in pore size in these vessels. A circulating macromolecule in human plasma in severe pre-eclampsia is therefore able to increase vascular permeability in an animal model. The nature of the circulating macromolecule is not known, except that it is, or is bound to, a molecule greater than 12 kDa.

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Evidence of impaired microvascular function in pre-eclampsia: a non-invasive study

Cited by 17 publications

References 22 publications

Von Willebrand Factor and ADAMTS13

Von Willebrand Factor and ADAMTS13

Microcirculation in women with severe pre‐eclampsia and HELLP syndrome: a case–control study

Plasma from women with severe pre-eclampsia increases microvascular permeability in an animal model in vivo

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