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PubMed: 26368565

Title
The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators.
Journal
PloS one
Volume
10
Issue
None
Pages
e0138111
Date
2015-01-01
Authors
Anderson UD | Edström-Hägerwall A | Gram M | Hansson SR | Johansson ME | Jälmby M | Larsson I | Åkerström B

Evidence d2e0b08b9e
JSON

This could be explained by the finding that CO induces vasodilation by binding to the heme-protein guanylyl cyclase [67].

a(CHEBI:"carbon monoxide") increases bp(MESH:Vasodilation) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Discussion

Evidence 820b21f222
JSON

In the extravascular compartment, cellular heme oxygenase (HO) is the most essential heme degrading protein, converting heme to free iron, biliverdin and CO [26,27].

deg(a(CHEBI:heme)) increases complex(a(CHEBI:"carbon monoxide"), a(CHEBI:"iron(2+)"), a(CHEBI:biliverdin)) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Placenta
Text Location
Introduction

p(HGNC:HMOX1) increases deg(a(CHEBI:heme)) View Subject | View Object

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Cell Ontology (CL)
hepatocyte
MeSH
Placenta
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Introduction

Evidence c819272665
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In line with previously published studies [13,14] the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE.

a(CHEBI:heme) positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
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Discussion

p(HGNC:AMBP) positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Discussion

path(MESH:"Pre-Eclampsia") positiveCorrelation p(HGNC:AMBP) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
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Discussion

path(MESH:"Pre-Eclampsia") positiveCorrelation a(CHEBI:heme) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Discussion

Evidence 736648044d
JSON

It was hypothesized that through the generation of reactive oxygen species (ROS), Hb induces oxidative damage to the placenta and a subsequent leakage over the blood-placental barrier [12].

a(MESH:"Fetal Hemoglobin") increases a(HM:"Oxidative damage") View Subject | View Object

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MeSH
Placenta
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Introduction

Evidence 0eff101645
JSON

A 4-fold increase of the HbF concentration was seen in the PE patients (p-value 0.01) as compared to the controls.

a(MESH:"Fetal Hemoglobin") positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Placenta
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Pre-Eclampsia") positiveCorrelation a(MESH:"Fetal Hemoglobin") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Placenta
MeSH
Pre-Eclampsia
Text Location
Results

Evidence c80e57094b
JSON

A negative correlation was found, i.e. an increased plasma cell-free HbF concentration was associated with a decreased plasma Hp concentration, when including all individuals, controls and women with PE (r = -0.335, p-value<0.0001, n = 145)(Fig 1A).

a(MESH:"Fetal Hemoglobin") negativeCorrelation p(HGNC:HP) View Subject | View Object

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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
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Results

p(HGNC:HP) negativeCorrelation a(MESH:"Fetal Hemoglobin") View Subject | View Object

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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
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Results

Evidence 4e05304f5a
JSON

Haptoglobin (Hp) is perhaps the most well investigated Hb-clearing molecule. It binds cell-free Hb in plasma [20,21] and the resulting Hp-Hb complex is cleared from blood via binding to the macrophage receptor CD163 [22].

a(MESH:"haptoglobin-hemoglobin complex") positiveCorrelation p(HGNC:HP) View Subject | View Object

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MeSH
Placenta
Text Location
Introduction

p(HGNC:CD163) decreases a(MESH:"haptoglobin-hemoglobin complex") View Subject | View Object

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MeSH
Placenta
Text Location
Introduction

p(HGNC:HP) positiveCorrelation a(MESH:"haptoglobin-hemoglobin complex") View Subject | View Object

Appears in Networks:
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MeSH
Placenta
Text Location
Introduction

Evidence e914f3b9b8
JSON

A statistically significant increase in the mean Hp-HbF concentration was observed for women with PE as compared to controls (p-value 0.018).

a(MESH:"haptoglobin-hemoglobin complex") positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Placenta
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Pre-Eclampsia") positiveCorrelation a(MESH:"haptoglobin-hemoglobin complex") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Placenta
MeSH
Pre-Eclampsia
Text Location
Results

Evidence 01250c93ec
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Correlation analysis using Pearson’s correlation coefficient showed statistically significant inverse correlation between Hpx and blood pressure, both systolic (r = -0.511, pvalue< 0.00001, n = 145) and diastolic (r = -0,520, p-value<0.00001, n = 145)(Fig 3).

bp(MESH:"Blood Pressure") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

p(HGNC:HPX) negativeCorrelation bp(MESH:"Blood Pressure") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

Evidence 9901eae99c
JSON

Analysis of the intravascular heme-scavenger protein Hpx showed a statistically significant decrease in plasma Hpx concentration of women with PE (p-value<0.0001) as compared to the controls (Table 3).

p(HGNC:HPX) negativeCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Pre-Eclampsia") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

Evidence f7fe06141a
JSON

Studies of sickle cell anemia patients have reported decreased levels of Hpx following hemolysis [68].

p(HGNC:HPX) negativeCorrelation path(MESH:"Anemia, Sickle Cell") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
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Discussion

path(MESH:"Anemia, Sickle Cell") negativeCorrelation p(HGNC:HPX) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
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Discussion

Evidence 99f3fa24be
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Soluble, shedded CD163, the macrophage receptor mediating elimination of the Hp-Hb complex, was analyzed in plasma [40–42]. The analysis showed a small but not statistically significant (p-value 0.37) increase in the PE group as compared to the controls (Table 3).

p(HGNC:CD163) positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Pre-Eclampsia") positiveCorrelation p(HGNC:CD163) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

Evidence f40f7379af
JSON

Analysis of the Hp concentration in plasma showed a statistically significant decrease in Hp concentration in plasma samples of women with PE as compared to controls (pvalue< 0.0001).

p(HGNC:HP) negativeCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Pre-Eclampsia") negativeCorrelation p(HGNC:HP) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

Evidence df33e05910
JSON

Furthermore, the plasmaand extravascular reductase and heme- and radical scavenger α1-microglobulin (A1M) binds and degrades free heme and can reduce metHb [28–30].

p(HGNC:AMBP) increases deg(a(CHEBI:heme)) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Placenta
Text Location
Introduction

Evidence afa0f96173
JSON

Analysis of plasma levels of the heme- and radical scavenger A1M showed a statistically significant increase of plasma A1M concentration in women with PE (p-value 0.035) as compared to controls (Table 3).

p(HGNC:AMBP) positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

path(MESH:"Pre-Eclampsia") positiveCorrelation p(HGNC:AMBP) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Plasma
MeSH
Pre-Eclampsia
Text Location
Results

Evidence 8615e842f9
JSON

Free heme in blood is sequestered by hemopexin (Hpx) [23,24] and the Hpx-heme complex is cleared from the circulation by the hepatocyte receptor CD91 [25].

p(HGNC:LRP1) decreases complex(a(CHEBI:heme), p(HGNC:HPX)) View Subject | View Object

Appears in Networks:
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Cell Ontology (CL)
hepatocyte
MeSH
Placenta
Text Location
Introduction

Evidence 38319694d2
JSON

The classical findings that define PE are hypertension and proteinuria appearing after 20 weeks of gestation.

path(MESH:"Pre-Eclampsia") positiveCorrelation path(MESH:Proteinuria) View Subject | View Object

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path(MESH:"Pre-Eclampsia") positiveCorrelation path(MESH:Hypertension) View Subject | View Object

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path(MESH:Hypertension) positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

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Introduction

path(MESH:Proteinuria) positiveCorrelation path(MESH:"Pre-Eclampsia") View Subject | View Object

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