Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin

May, Karen; Rosenlöf, Lena Wester; Olsson, Magnus; Centlow, Magnus; Mörgelin, Matthias; Larsson, Inger; Cederlund, Martin; Rutardóttir, Sigurbjörg; Siegmund, Werner; Schneider, H.; Åkerström, Bo; Hansson, Stefan R.

doi:10.1016/j.placenta.2011.01.017

Cited by 76 publications

(98 citation statements)

References 54 publications

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“…It is often co-localized with elastin and collagen [31][32][33] and binds to collagen in vitro [34]. A distribution of A1M at various interfaces between the cells of the body and the ambient environment (blood/tissue, air/tissue, intestinal lumen/villi), as well as at the interface between maternal blood and fetal tissues in placenta [35,36], is consistent with a protective role of A1M in vivo (see below).…”

Section: Distributionmentioning

confidence: 61%

“…While ex vivo perfusion with Hb in the fetal circulation led to a significant increase of the perfusion pressure, feto-maternal leakage of Hb, morphological damage, and up-regulation of genes related to immune response, apoptosis, and oxidative stress, simultaneous addition of A1M to the maternal circulation abrogated the Hb leakage ( Figure 5D), morphological damage ( Figure 6B) and gene up-regulation [36].…”

Section: Organ Models: Protection Of Skin Explants and Ex Vivo Perfusmentioning

confidence: 98%

“…The protective effects of A1M have been studied in skin explants and in a perfused placenta model [32,36]. In the skin explants, exogenously added A1M inhibited the heme-induced ultrastructural damage ( Figure 5A-C), up-regulation of antioxidation-and cell cycle regulatory genes, and formation of protein carbonyl groups, a marker of oxidative stress [32].…”

Section: Organ Models: Protection Of Skin Explants and Ex Vivo Perfusmentioning

confidence: 99%

“…has been described to be widely distributed in placenta cells and matrix [35,46], and its protective effects were investigated in the placenta perfusion model [36]. This model enables studies of cell-and matrix structure and functions including the feto-maternal barrier [58].…”

Section: Organ Models: Protection Of Skin Explants and Ex Vivo Perfusmentioning

confidence: 99%

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A1M, an extravascular tissue cleaning and housekeeping protein

Åkerström¹,

Gram²

2014

Free Radical Biology and Medicine

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Section: Distributionmentioning

confidence: 61%

Section: Organ Models: Protection Of Skin Explants and Ex Vivo Perfusmentioning

confidence: 98%

Section: Organ Models: Protection Of Skin Explants and Ex Vivo Perfusmentioning

confidence: 99%

Section: Organ Models: Protection Of Skin Explants and Ex Vivo Perfusmentioning

confidence: 99%

See 2 more Smart Citations

A1M, an extravascular tissue cleaning and housekeeping protein

Åkerström¹,

Gram²

2014

Free Radical Biology and Medicine

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“…The ex vivo dual recirculating human placental perfusion model provides a controlled and reliable system for studying the placental transport of various endogenous and exogenous compounds 3,11,12,18,19 and a wide range of other functions of the placenta like mechanisms responsible for the development of pathological states like preeclampsia [20][21][22] . In this protocol we focus mainly on the set up, handling and method that allow the study of accumulation, effects and translocation rates of a broad set of xenobiotics or nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

Grafmüller

Manser

Krug

et al. 2013

JoVE

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Decades ago the human placenta was thought to be an impenetrable barrier between mother and unborn child. However, the discovery of thalidomide-induced birth defects and many later studies afterwards proved the opposite. Today several harmful xenobiotics like nicotine, heroin, methadone or drugs as well as environmental pollutants were described to overcome this barrier. With the growing use of nanotechnology, the placenta is likely to come into contact with novel nanoparticles either accidentally through exposure or intentionally in the case of potential nanomedical applications. Data from animal experiments cannot be extrapolated to humans because the placenta is the most species-specific mammalian organ 1 . Therefore, the ex vivo dual recirculating human placental perfusion, developed by Panigel et al. in 1967 2 and continuously modified by Schneider et al. in 1972 3 , can serve as an excellent model to study the transfer of xenobiotics or particles.Here, we focus on the ex vivo dual recirculating human placental perfusion protocol and its further development to acquire reproducible results.The placentae were obtained after informed consent of the mothers from uncomplicated term pregnancies undergoing caesarean delivery. The fetal and maternal vessels of an intact cotyledon were cannulated and perfused at least for five hours. As a model particle fluorescently labelled polystyrene particles with sizes of 80 and 500 nm in diameter were added to the maternal circuit. The 80 nm particles were able to cross the placental barrier and provide a perfect example for a substance which is transferred across the placenta to the fetus while the 500 nm particles were retained in the placental tissue or maternal circuit. The ex vivo human placental perfusion model is one of few models providing reliable information about the transport behavior of xenobiotics at an important tissue barrier which delivers predictive and clinical relevant data. Video LinkThe video component of this article can be found at

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Elevated levels of protein AMBP in cerebrospinal fluid of women with preeclampsia compared to normotensive pregnant women

Berg

Duvekot

Güzel³

et al. 2016

Prot. Clin. Appl.

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The current study showed a clear difference between the protein profiles of CSF from patients with PE and normotensive pregnant women. Protein AMBP is a precursor of a heme-binding protein that counteracts the damaging effects of free hemoglobin, which may be related to the presence of free hemoglobin in CSF. Protein levels showed correlations with clinical symptoms during pregnancy and postpartum. To our knowledge, this is the first LC-MS/MS proteome profiling study on a unique set of CSF samples from (severe) preeclamptic patients and normotensive pregnant women.

show abstract

Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin

Cited by 76 publications

References 54 publications

A1M, an extravascular tissue cleaning and housekeeping protein

A1M, an extravascular tissue cleaning and housekeeping protein

Determination of the Transport Rate of Xenobiotics and Nanomaterials Across the Placenta using the <em>ex vivo</em> Human Placental Perfusion Model

Elevated levels of protein AMBP in cerebrospinal fluid of women with preeclampsia compared to normotensive pregnant women

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