Endothelial pathology in preeclampsia

Turner, R.J. (2018)

Doctoral Thesis

Preeclampsia is a syndrome of pregnancy characterised by hypertension and proteinuria and occurs in up to 5 percent of pregnant women. The pathophysiology of preeclampsia has not been fully elucidated yet. The endothelium is known to play a key role in the pathogenesis and levels of vascular endothelial growth factor are decreased due to an angiogenic imbalance. In the first part of this thesis, genes associated with preeclampsia were investigated through meta-analysis; genes within the coagulation and immunology domains remained significantly associated with preeclampsia after meta-analysis. In the second and third part of this thesis, the possible role of a key regulator of coagulation and immunology on the endothelium, thrombomodulin, in preeclampsia was investigated in the placenta and the kidney. Diminished placental thrombomodulin expression was associated with the angiogenic imbalance of preeclampsia. Next, in the fourth part of this thesis the interplay between podocytes and endothelial cells in the glomerulus during the anti-angiogenic conditions in preeclampsia was reviewed. In the final part of this thesis the splicing pattern of vascular endothelial growth factor was investigated throughout different examples of glomerular disease.

• Preeclampsia
• Pathology
• Glomerulus
• Podocytes
• Vascular endothelial growth factor
• Alternative splicing
• Soluble Flt1
• Thrombomodulin

• All authors: Turner, R.J.
• Supervisor: Bruijn, J.A.; Bloemenkamp, K.W.M.
• Co-supervisor: Baelde, J.J.
• Committee: Smit, V.T.H.B.M.; Groot, C.J.M. de; Goor, H. van
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2018-09-05
• ISBN (print): 9789402810875