Vascular Endothelial Growth Factor Ligands and Receptors That Regulate Human Cytotrophoblast Survival Are Dysregulated in Severe Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome
Identifieur interne : 009340 ( Main/Exploration ); précédent : 009339; suivant : 009341Vascular Endothelial Growth Factor Ligands and Receptors That Regulate Human Cytotrophoblast Survival Are Dysregulated in Severe Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Low Platelets Syndrome
Auteurs : Yan Zhou ; Michael Mcmaster ; Kirstin Woo ; Mary Janatpour ; Jean Perry ; Terhi Karpanen ; Kari Alitalo [Finlande] ; Caroline Damsky ; Susan J. FisherSource :
- The American Journal of Pathology [ 0002-9440 ] ; 2002.
Abstract
Human placental development combines elements of tumorigenesis and
vasculogenesis. The organ’s specialized epithelial cells,
termed cytotrophoblasts, invade the uterus where they reside in
the interstitial compartment. They also line uterine arteries and
veins. During invasion, ectodermally derived cytotrophoblasts
undergo pseudovasculogenesis, switching their adhesion molecule
repertoire to mimic that of vascular cells. Failures in this
transformation accompany the pregnancy complication preeclampsia.
Here, we used a combination of
Url:
PubMed: 11943725
PubMed Central: 3277330
Affiliations:
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Le document en format XML
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Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Low Platelets
Syndrome</title>
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<front><div type="abstract" xml:lang="en"><p>Human placental development combines elements of tumorigenesis and
vasculogenesis. The organ’s specialized epithelial cells,
termed cytotrophoblasts, invade the uterus where they reside in
the interstitial compartment. They also line uterine arteries and
veins. During invasion, ectodermally derived cytotrophoblasts
undergo pseudovasculogenesis, switching their adhesion molecule
repertoire to mimic that of vascular cells. Failures in this
transformation accompany the pregnancy complication preeclampsia.
Here, we used a combination of <italic>in situ</italic>
and
<italic>in vitro</italic>
analyses to characterize the cell’s expression
of vascular endothelial growth factor (VEGF) family ligands and
receptors, key regulators of conventional vasculogenesis
and angiogenesis. Cytotrophoblast differentiation and invasion during
the first and second trimesters of pregnancy were associated with
down-regulation of VEGF receptor (VEGFR)-2. Invasive cytotrophoblasts
in early gestation expressed VEGF-A, VEGF-C, placental
growth factor (PlGF), VEGFR-1, and VEGFR-3 and,
at term, VEGF-A, PlGF, and VEGFR-1. <italic>In
vitro</italic>
the cells incorporated VEGF-A into the surrounding
extracellular matrix; PlGF was secreted. We also found that
cytotrophoblasts responded to the VEGF ligands they produced. Blocking
ligand binding significantly decreased their expression of integrin
α1, an adhesion molecule highly expressed by endovascular
cytotrophoblasts, and increased apoptosis. In severe
preeclampsia and hemolysis, elevated liver enzymes, and
low platelets syndrome, immunolocalization on tissue sections
showed that cytotrophoblast VEGF-A and VEGFR-1 staining decreased;
staining for PlGF was unaffected. Cytotrophoblast secretion of the
soluble form of VEGFR-1 <italic>in vitro</italic>
also increased.
Together, the results of this study showed that VEGF family
members regulate cytotrophoblast survival and that expression of
a subset of family members is dysregulated in severe forms of
preeclampsia.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Finlande</li>
</country>
<region><li>Uusimaa</li>
</region>
<settlement><li>Helsinki</li>
</settlement>
<orgName><li>Université d'Helsinki</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Damsky, Caroline" sort="Damsky, Caroline" uniqKey="Damsky C" first="Caroline" last="Damsky">Caroline Damsky</name>
<name sortKey="Fisher, Susan J" sort="Fisher, Susan J" uniqKey="Fisher S" first="Susan J." last="Fisher">Susan J. Fisher</name>
<name sortKey="Janatpour, Mary" sort="Janatpour, Mary" uniqKey="Janatpour M" first="Mary" last="Janatpour">Mary Janatpour</name>
<name sortKey="Karpanen, Terhi" sort="Karpanen, Terhi" uniqKey="Karpanen T" first="Terhi" last="Karpanen">Terhi Karpanen</name>
<name sortKey="Mcmaster, Michael" sort="Mcmaster, Michael" uniqKey="Mcmaster M" first="Michael" last="Mcmaster">Michael Mcmaster</name>
<name sortKey="Perry, Jean" sort="Perry, Jean" uniqKey="Perry J" first="Jean" last="Perry">Jean Perry</name>
<name sortKey="Woo, Kirstin" sort="Woo, Kirstin" uniqKey="Woo K" first="Kirstin" last="Woo">Kirstin Woo</name>
<name sortKey="Zhou, Yan" sort="Zhou, Yan" uniqKey="Zhou Y" first="Yan" last="Zhou">Yan Zhou</name>
</noCountry>
<country name="Finlande"><region name="Uusimaa"><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name>
</region>
</country>
</tree>
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