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Extracellular Matrix Remodeling of the Umbilical Cord and Placenta in Preeclampsia

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2013 by Ayse Kirbas, Zekai Tahir Burak Maternity and Teaching Hospital.
Recruitment status was:  Recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01931891
First Posted: August 29, 2013
Last Update Posted: August 30, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Turgut Ozal University
Information provided by (Responsible Party):
Ayse Kirbas, Zekai Tahir Burak Maternity and Teaching Hospital
  Purpose

Preeclampsia affects 2% to 8% of all pregnancies and is a major cause of maternal morbidity an mortality worldwide.Althought the primary pathology leading to preeclampsia is remain not known, complex pathophysiologic pathways and mechanisms have been described.

New blood vessels evolve during angiogenesis and vasculogenesis, two physiological processes, that play a crucial role in embryogenesis and placentation. Structural alterations in the human umbilical cord, maternal spiral arteries can cause adverse fetal consequences.Pre-eclampsia is accompanied by an extensive remodelling of the ECM of the umbilical cord. Pre-eclamptic Wharton's jelly contains higher amounts of glycosaminoglycans in comparison to control tissue.

Matrixmetalloproteinases (MMPs) are a family of proteolytic enzymes that degrade various components of the extracellular matrix (ECM). A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). Dysregulation of ADAMs and ADAMTS expression have been reported in different types of pathologies such as cancer, osteoarthritis, neurodegenerative inflammation or asthma.

The role of ADAMTS in the pathomechanism of pre-eclampsia has not been studied until now. We therefore decided to compare the ADAMTS composition of the umbilical cord and placenta from newborns of mothers with pre-eclampsia with those with normal pregnancy.


Condition
Alterations of ECM in Umbilical Cord ECM in Preeclampisa Alterations of ECM in Placenta in Preeclampisa

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional

Resource links provided by NLM:


Further study details as provided by Ayse Kirbas, Zekai Tahir Burak Maternity and Teaching Hospital:

Primary Outcome Measures:
  • severe preclampsia [ Time Frame: 34 weeks ]

Biospecimen Retention:   Samples With DNA
umbilical cord placenta

Estimated Enrollment: 20
Study Start Date: July 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
prreclampsia

  Hide Detailed Description

Detailed Description:

Preeclampsia is a multi-systemic disorder. Despite its seriousness, the aetyology remains unknown. Current theories include abnormal placentation, cardiovascular maladaptation to pregnancy, genetic and immune mechanisms, angiogenic factors and an enhanced systemic inflammatory response. Poor placental perfusion leading to wide spread maternal endothelial dysfunction is accepted as a major mechanism.

The trophoblastic invasion of maternal vessels results many changes in extracellular matrix, which gives rise to high uteroplacental vessel distensibility to accommodate the increased blood flow. So, İn normal pregnancy, there is a wide spread vasodilatation, with increased arterial compliance and reduced peripheral vascular resistance.In preeclampsia, however, trophoblastic invasion is reduced, leading to incomplete modification of maternal spiral arteries and therefore to decreases in placental perfusion.

Pre-eclampsia is accompanied by an extensive remodelling of the ECM of the umbilical cord and placenta. Pre-eclamptic Wharton's jelly contains higher amounts of glycosaminoglycans in comparison to control tissue.

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade various components of the extracellularmatrix (ECM). These enzymes play an essential role in physiological states such as tissue remodeling, morphogenesis and wound healing anda lso in pathological processes such as tumor cell invasion and metastasis.

A Disintegrin And Metalloproteinases (ADAMs) and ADAMs with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix Metalloproteinases (MMPs). Dysregulation of ADAMsexpression has beenreported in differenttypes of pathologies such as cancer, osteoarthritis, neurodegenerative inflammation or asthma.

Some authors suggestted that ADAM-8, -9, -10, -12, -15, -17, and ADAMTS-1 might play roles in uterus remodeling during the periimplantation period and ADAMTS-12, independent of its proteolytic activity, plays a critical role in human trophoblastic cell invasion in vitro.

Human umbilical cord is an extra-embryonic structure linking the mother and fetus during pregnancy In the umbilical cord two arteries and one vein are surrounded by a collagen-rich, myxomatous substance, called Wharton's jelly (WJ) that protect the umbilical vessels against extension, bending, twisting and compression.

The extracellular matrix (ECM) of WJ is very copious and contains significant amounts of hyaluronic acid and some sulphated glycosaminoglycans (GAGs). İts interesting that Wharton's jelly contain a low number of cells but large amounts of collagen and GAGs. Wharton's jelly plays also an important role as a storage for some compounds, such as growth factor. Previous studies demonstrated that both human umbilical cord serum and tissues contain large amounts of IGF-I and IGF-binding proteins (BPs), mainly BP-1 and BP-3.

Structural alterations in the human umbilical cord can cause adverse fetal consequences. ECM dynamics can result from changes of ECM composition, for example, because of altered synthesis or degradation of one or more ECM components, or in architecture because of altered organization. Pre-eclampsia is accompanied by an extensive remodelling of the ECM of the umbilical cord.

İt found that significant increase in collagen content in the umbilical cord arteries and vein and premature replacement of hyaluronic acid by sulfated GAGs both in the UCAs and in Wharton's jelly in preeclampsia. Pre-eclamptic Wharton's jelly contains higher amounts of glycosaminoglycans in comparison to control tissue.

The role of ADAMTS in the pathology of pre-eclampsia has not been studied until now. We therefore decided to compare the ADAMTS composition of the umbilical cord and placenta from newborns of mothers with pre-eclampsia with those with normal pregnancy.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 39 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
preeclamptic women
Criteria

Inclusion Criteria:

Clinical diagnosis of preeclampsia (diagnosed per ACOG criteria)

Exclusion Criteria:

known chronic disease multipl pregnancies

Exclusion Criteria:

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01931891


Contacts
Contact: ayse kirbas, md 533-646-9213 ayseozdemirkirbas@hotmail.com

Locations
Turkey
Zekai Tahir Burak Maternity Hospital Recruiting
Ankara, Turkey
Contact: nuri danisman, md    306-5000      
Principal Investigator: ayse kirbas, md         
Sponsors and Collaborators
Zekai Tahir Burak Women's Health Research and Education Hospital
Turgut Ozal University
Investigators
Principal Investigator: ayse kirbas, md zekai tahir burak hospital
  More Information

Responsible Party: Ayse Kirbas, Zekai Tahir Burak Maternity and Teaching Hospital
ClinicalTrials.gov Identifier: NCT01931891     History of Changes
Other Study ID Numbers: ztb- wharton jelly
First Submitted: August 26, 2013
First Posted: August 29, 2013
Last Update Posted: August 30, 2013
Last Verified: July 2013

Keywords provided by Ayse Kirbas, Zekai Tahir Burak Maternity and Teaching Hospital:
preeclampsia, ADAMTS , wharton jelly, extracellüler matrix, placenta

Additional relevant MeSH terms:
Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications