Short summary

The pathophysiology of preeclampsia (PE) is still unknown and the ultimate treatment is to terminate the pregnancy preterm. Very little is also known about the relation between pregnancy with or without PE and the Contact Activation System (CAS). 

The study will contribute substantially to the understanding of the role of CAS in the pathophysiology of PE. Inhibitors of CAS may potentially be used in the treatment of PE if activation of CAS plays significant roles in the development of the disease. This hopefully means that preterm birth due to PE can be reduced.

Rationale

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 

- To investigate the initiation, propagation, and inhibition of CAS in women with PE in comparison with a matching group of pregnant women without PE.

- To investigate the impact of misfolded PAI-2 on CAS.

- To develop immunochemical assays for determination of native and misfolded PAI-2 in human plasma.

- To assess the plasma concentration of native and misfolded PAI-2 in women with PE and matching controls

Description of the cohort

Pregnant women with and without preeclampsia

Data and biological material

Blood.

Publications associated with the project

Department of Clinical Biochemistry, Hospital of South West Denmark and Unit for Thrombosis Research, University of Southern Denmark

• Professor and Consultant Jørgen Gram 
• Associate ,PhD Johannes Sidelmann

Department of Gynaecology and Obstetrics, Oden se University Hospital

• Professor and Consultant Jan Stener 

Unit for Thrombosis Research, Department of Health and Department of Cancer and Inflammation, University of Southern Denmark, Odense

• Senior Researcher/Associate professor Yaseelan Palarasah