Preeclampsia is an acute emergent hypertensive “target-organ” condition of pregnancy, characterized by hypertension and proteinuria. It affects 3-10% of all pregnancies worldwide. Preeclampsia is a major health problem, responsible for approximately 50 000 maternal deaths annually. Women who develop preeclampsia and children of preeclamptic pregnancies are at increased risk of coronary heart disease, stroke and cardiovascular disease in later life. The cause of preeclampsia is unknown.
Our research program on this disease involves patient-oriented and basic research studies, including animal models. Our primary focus has been on understanding Cytochrome P450-related mechanisms, angiogenesis and auto-antibodies (renin-angiotensin system). Agonistic auto-antibodies to the angiotensin II receptor type I (AT1-AA) have been identified in preeclamptic mothers and fetus, and induce signal transduction including protein kinase C and the mitogen-activated protein pathway, resulting in the activation of transcription factors NF-kB and AP-1. We have identified AT1-AA in various rat models of preeclampsia. Subsequently we have provided experimental in vivo evidence that AT1-AA account for the observed reduction in Ang II sensitivity observed in preeclamptic patients. We are also investigating new therapeutic targets in a transgenic rat model that features key characteristics of preeclampsia. With this rat model we have established state of the art diagnostic procedures, routinely performed in the clinic for pregnant women, enabling us to show a causal link between reduced trophoblast invasion and placental perfusion. In clinical studies, we are currently investigating physiological parameters and identifying novel biomarkers during and after preeclampsia, which may help to explain the increased cardiovascular risk of former preeclamptic patients. Besides AT1 receptor antibodies, we are also investigating the role of ANP, GDF-15, sFlt1 and CRP. Präeklampsie, Berlin
Kvehaugen AS, Melien O, Holmen OL, Laivuori H, Oian P, Andersgaard AB, Dechend R, Staff AC.
Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia.
Hypertension. 2013 Jan 21.
Herse F, Lamarca B, Hubel CA, Kaartokallio T, Lokki AI, Ekholm E, Laivuori H, Gauster M, Huppertz B, Sugulle M, Ryan MJ, Novotny S, Brewer J, Park JK, Kacik M, Hoyer J, Verlohren S, Wallukat G, Rothe M, Luft FC, Muller DN, Schunck WH, Staff AC, Dechend R.
CYP2J2 Expression and Circulating Epoxyeicosatrienoic Metabolites in Preeclampsia.
Circulation. 2012 Dec 18;126(25):2990-9.
Novotny SR, Wallace K, Heath J, Moseley J, Dhillon P, Weimer A, Wallukat G,Herse F,Wenzel K, Martin JN Jr, Dechend R, Lamarca B.
Activating autoantibodies to the angiotensin II type I receptor play an important role in mediating hypertension in response to adoptive transfer of CD4+ T lymphocytes from placental ischemic rats.
Am J Physiol Regul Integr Comp Physiol. 2012 May 15;302(10):R1197-201. Epub 2012 Mar 28.
Dhillion P, Wallace K, Herse F, Scott J, Wallukat G, Heath J, Mosely J, Martin JN Jr, Dechend R, Lamarca B.
IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy.
Am J Physiol Regul Integr Comp Physiol. 2012 Aug;303(4):R353-8. Epub 2012 Jun 20.
Jensen F, Wallukat G,Herse F, Budner O, El-Mousleh T, Costa SD, Dechend R, Zenclussen AC.
CD19+CD5+ Cells as Indicators of Preeclampsia.
Hypertension. 2012 Feb 21.
Herse F*, Sugulle M,Hering L, Mockel M,Dechend R, Staff AC.
Cardiovascular biomarker midregional proatrial natriuretic Peptide during and after preeclamptic pregnancies.
Hypertension. 2012 Feb;59(2):395-401. Epub 2011 Dec 19.
Searle J, Mockel M, Gwosc S, Datwyler SA,Qadri F, Albert GI, Holert F, Isbruch A, Klug L,Muller DN, Dechend R, Muller R, Vollert JO, Slagman A, Mueller C, Herse F.
Heparin strongly induces soluble fms-like tyrosine kinase 1 release in vivo and in vitro--brief report.
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2972-4. Epub 2011 Oct 6.
Kvehaugen AS, Dechend R, Ramstad HB, Troisi R, Fugelseth D, Staff AC.
Endothelial function and circulating biomarkers are disturbed in women and children after preeclampsia
Hypertension. 2011 Jul;58(1):63-9.
Herse F, Lamarca B.
Angiotensin II Type 1 Receptor Autoantibody (AT1-AA)-Mediated Pregnancy Hypertension.
Am J Reprod Immunol. 2012 Dec 28.
Staff AC,Dechend R, Redman CW.
Review: Preeclampsia, acute atherosis of the spiral arteries and future cardiovascular disease: Two new hypotheses.
Placenta. 2012 Dec 13.
Dechend R, Staff AC
Placenta messages to the mother: not just debris.
Hypertension. 2012 Feb;59(2):191-3.
Verlohren S, Stepan H, Dechend R.
Angiogenic growth factors in the diagnosis and prediction of pre-eclampsia.
Clin Sci (Lond). 2012 Jan;122(2):43-52.