Abstract
Preeclampsia is one of the most frequent and severe complications of pregnancy. Symptoms of preeclampsia usually occur after 20 weeks of pregnancy and include hypertension and kidney dysfunction with proteinuria. Up to now, delivery of the infant has been the most effective and life-saving treatment to alleviate symptoms of preeclampsia because a causative treatment does not exist, which could prolong a pregnancy complicated with preeclampsia. Preeclampsia is a complex medical condition, which is attributed to a variety of different risk factors and causes. Risk factors account for insufficient placentation and impaired vasculogenesis and finally culminate in this life-threatening condition of pregnancy. Despite progress, many pathomechanisms and causes of preeclampsia are still incompletely understood. In recent years, it was found that excessive protein complex formation between G-protein-coupled receptors is a common sign of preeclampsia. Specifically, the aberrant heteromerization of two vasoactive G-protein-coupled receptors (GPCRs), the angiotensin II AT1 receptor and the bradykinin B2 receptor, is a causative factor of preeclampsia symptoms. Based on this knowledge, inhibition of abnormal GPCR protein complex formation is an experimental treatment approach of preeclampsia. This review summarizes the impact of pathological GPCR protein aggregation on symptoms of preeclampsia and delineates potential new therapeutic targets.
Highlights
Monitoring of blood pressure during pregnancy is an important measure of diagnosis because high blood pressure which exceeds 140/90 mm Hg is a common symptom of preeclampsia [3]
A protein complex formed by GPCR heteromerization was documented to be a sufficient cause of preeclampsia [14]. This protein complex consists of two G-protein-coupled receptors, which are known to regulate vascular tone, i.e., the angiotensin II AT1 receptor, AGTR1, and the bradykinin B2 receptor, BDKRB2 [15,16]
The protein beta-arrestin1 could support the down-regulation of pathological GPCR aggregates by a beta-arrestin-mediated mechanism [14]. Based on these findings, ongoing research efforts aim to develop a treatment of acute preeclampsia symptoms and/or late cardiovascular preeclampsia complications by inhibition of disease-causing GPCR protein aggregation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. While acute preeclampsia symptoms subside after delivery, a pregnancy complicated with preeclampsia is associated with an increased risk of cardiovascular disease, hypertension and renal dysfunction later in life, for the mother and the infant [6,7]. A protein complex formed by GPCR heteromerization was documented to be a sufficient cause of preeclampsia [14] This protein complex consists of two G-protein-coupled receptors, which are known to regulate vascular tone, i.e., the angiotensin II AT1 receptor, AGTR1, and the bradykinin B2 receptor, BDKRB2 [15,16]. The protein beta-arrestin could support the down-regulation of pathological GPCR aggregates by a beta-arrestin-mediated mechanism [14] Based on these findings, ongoing research efforts aim to develop a treatment of acute preeclampsia symptoms and/or late cardiovascular preeclampsia complications by inhibition of disease-causing GPCR protein aggregation. This review gives an overview of approaches to target symptoms of preeclampsia by interference with pathological GPCR protein aggregation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
