[Frontiers In Bioscience, Landmark, 24, 1462-1476, June 1, 2019]

Regulatory antibodies against GPCR in women ten years after early-onset preeclampsia

Anna Birukov1,2,3,4,5, Hella E.C. Muijsers6, Harald Heidecke7, José T. Drost8, Mark W. Cunnigham Jr.9, Kristin Kraker1,2,3,4,5, Nadine Haase1,2,3,4,5, Alina Frolova10, Dominik N. Müller1,2,3,4,5, Florian Herse1,3,4,5, Angela H.E.M. Maas6, Ralf Dechend1,2,3,4,5,11

1Experimental and Clinical Research Center, a joint cooperation between Max-Delbrück-Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 2DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany; 3Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 4Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; 5Berlin Institute of Health (BIH), Berlin, Germany; 6Radboud University Medical Center, Department of Cardiology, Nijmegen, The Netherlands; 7CellTrend GmbH, Luckenwalde, Germany; 8Saxenburgh Group, department cardiology, Hardenberg, The Netherlands; 9University of Mississippi Medical Center, Department of Pharmacology & Toxicology, Jackson, Mississippi, USA; 10Institute of Molecular Biology and Genetics of NASU, Kyiv, Ukraine; 11Department of Cardiology and Nephrology, HELIOS Klinikum Berlin, Berlin, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Methods
3.1. Study population
3.2. Laboratory analyses
3.3 Statistical analyses
4. Results
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Preeclampsia is associated with an increased cardiovascular risk later in life. Anti-GPCR autoantibodies have been shown to contribute to the development of cardiovascular disease. We investigated whether anti-GPCR autoantibodies are elevated in women with a history of early-onset preeclampsia 8-11 years postpartum, and whether they correlate with clinical outcomes. We investigated data from the Preeclampsia Risk EValuation in FEMales cohort, a retrospective matched case-control study. Anti AT1R-, beta1AR-, ETAR-, PAR1- and CXCR3- autoantibodies were determined in 485 samples by using commercially available ELISA. Women with the lowest combined levels of autoantibodies and a history of early preeclampsia had significantly higher SBP, DBP and MAP (all p<0.001) compared to the controls. The individual titer levels of autoantibodies were not different between controls and former early PE groups 8-11 years postpartum. In conclusion, regulatory autoantibodies alone are not sufficient to explain hypertension or other cardiovascular pathologic conditions, but together with other risk factors such as a previous hypertensive pregnancy, lower levels of autoantibodies are associated with increased blood pressure.

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Key Words: Autoantibodies against GPCR, Preeclampsia, Adverse pregnancy outcome, Blood pressure, Cardiovascular risk

Send correspondence to: Ralf Dechend, MD, Experimental and Clinical Research Center (ECRC), Lindenberger Weg 80, 13125 Berlin, Germany, Tel:  49 30 450 540301, Fax: 49-30-450540944, E-mail: ralf.dechend@charite.de