CAS, Misfolding Disease, Protein, Preeclampsia
Conditions
Keywords
Contact activation system, PAI-2
Brief 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.
Interventions
OTHERPregnancy
Pregnancies complicated by preeclampsia
Sponsors
Region of Southern Denmark
OPEN
Lida og Oskar Nielsens Fond
Esbjerg Fonden
Gangsted Fonden
University of Southern Denmark
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Inclusion criteria
* Pregnant women developing preeclampsia
Exclusion criteria
* Healthy pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Contact Activation System (CAS) | 3 years | Biomarkers for the CAS in plasma Coagulation factor XII antigen/activity, High molecular weight kininogen (HK), Truncated (HK), Prekallikrein antigen, kallikrein generation, C1-esterase inhibitor, alpha-2-macroglobulin, Fast form alpha-2-macroglobulin, Thrombin generation, |
| Misfolded Plasminogen activator inhibitor 2 (PAI-2) | 3 years | Biomarkers for misfolded PAI-2 in plasma Native PAI-2 antigen, Misfolded PAI-2, Native PAI-1 antigen, |
Countries
Denmark
Outcome results
None listed