Preeclampsia and Contact Activation

Summary

Preeclampsia (PE) affects approximately 5% of all pregnancies with 2,500 cases registered annually in Denmark. PE is characterized by incomplete modelling of the spiral arteries of the uterus, hypertension, inflammation, hypercoagulability and proteinuria. Neonatal complications and increased cardiovascular risk are common features of the syndrome.

PE shares pathophysiologic features with recognized protein misfolding disorders and misfolded proteins are present in urine from women with PE. Misfolded proteins are potent activators of the contact system (CAS) which is involved in inflammation, coagulation and fibrinolysis.

Plasminogen activator inhibitor 2 (PAI-2) regulates important fibrinolytic processes in the placenta. The oxidative milieu characterizing PE may trigger misfolding of PAI-2 which then loose inhibitory capacity, but gain CAS-activating capacity. Thus, misfolding of PAI-2 may affect the fibrinolytic system in the placenta and compromise the modelling of the spiral arteries. Moreover, misfolded PAI-2 may contribute to the hypercoagulability and the inflammatory conditions characterizing women with PE.

The aim of the present study is i) to characterize CAS in women with PE, ii) to study the CAS-activating capacity of misfolded PAI-2 and iii) to develop and apply immunochemical methods for determination of native and misfolded PAI-2 in plasma.

Conditions

• Preeclampsia
• CAS
• Misfolding Disease, Protein

Interventions

OTHER

Pregnancy

Pregnancies complicated by preeclampsia

Sponsors & Collaborators

• Region of Southern Denmark

  collaborator OTHER

• OPEN

  collaborator UNKNOWN

• Lida og Oskar Nielsens Fond

  collaborator UNKNOWN

• Esbjerg Fonden

  collaborator OTHER

• Gangsted Fonden

  collaborator UNKNOWN

• University of Southern Denmark

  lead OTHER

Principal Investigators

• Jørgen B Gram, Professor · University of Southern Denmark

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-01-20

Primary Completion

2021-11-30

Completion

2021-11-30

Countries

• Denmark

Study Locations