Pathological AT1R-B2R Protein Aggregation and Preeclampsia

Quitterer, Ursula; AbdAlla, Said

doi:10.3390/cells10102609

Cited by 5 publications

(8 citation statements)

References 144 publications

(388 reference statements)

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“…AT 1 R with PAR1 ( 138 ), μOR ( 139 ), prostaglandin F2aR ( 140 ), ET B R ( 141 ), RXFP1 ( in vivo ( 142 , 143 )), ADRB2 ( 144 ), AT 2 R ( 145 ), CB 1 R ( 146 ), secretin receptor (SCTR, class B) ( 147 ), bradykinin B 2 R ( 148 );…”

Section: Implications For Receptor Oligomerization and Heteromer Arra...mentioning

confidence: 99%

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

et al. 2022

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In conjunction with the endothelin (ET) type A (ETAR) and type B (ETBR) receptors, angiotensin (AT) type 1 (AT1R) and type 2 (AT2R) receptors, are peptide-binding class A G-protein-coupled receptors (GPCRs) acting in a physiologically overlapping context. Angiotensin receptors (ATRs) are involved in regulating cell proliferation, as well as cardiovascular, renal, neurological, and endothelial functions. They are important therapeutic targets for several diseases or pathological conditions, such as hypertrophy, vascular inflammation, atherosclerosis, angiogenesis, and cancer. Endothelin receptors (ETRs) are expressed primarily in blood vessels, but also in the central nervous system or epithelial cells. They regulate blood pressure and cardiovascular homeostasis. Pathogenic conditions associated with ETR dysfunctions include cancer and pulmonary hypertension. While both receptor groups are activated by their respective peptide agonists, pathogenic autoantibodies (auto-Abs) can also activate the AT1R and ETAR accompanied by respective clinical conditions. To date, the exact mechanisms and differences in binding and receptor-activation mediated by auto-Abs as opposed to endogenous ligands are not well understood. Further, several questions regarding signaling regulation in these receptors remain open. In the last decade, several receptor structures in the apo- and ligand-bound states were determined with protein X-ray crystallography using conventional synchrotrons or X-ray Free-Electron Lasers (XFEL). These inactive and active complexes provide detailed information on ligand binding, signal induction or inhibition, as well as signal transduction, which is fundamental for understanding properties of different activity states. They are also supportive in the development of pharmacological strategies against dysfunctions at the receptors or in the associated signaling axis. Here, we summarize current structural information for the AT1R, AT2R, and ETBR to provide an improved molecular understanding.

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Section: Implications For Receptor Oligomerization and Heteromer Arra...mentioning

confidence: 99%

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

et al. 2022

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“…La incorporación de la aspirina (AAS) ha sido bastante debatida. Los datos primarios en el año 1985 mostraron la inicial prueba de que el AAS a bajas dosis alcanzaría aplazar los indicios de la preeclampsia, donde transitaron más de 30 años hasta que monumentales ensayos controlados con placebo consiguieron certificar la utilidad terapéutica de la aspirina para prevenir la enfermedad hipertensiva en embarazos de elevado riesgo (Quitterer & AbdAlla, 2021).…”

Section: Beneficiosunclassified

“…La aspirina inhibe la ciclooxigenasa (COX). Al disminuir el tromboxano (TXA2), modifica la relación PGI2/TXA2, reestableciéndose el balance fisiológico alterado por la invasión trofoblástica fallida (Quitterer & AbdAlla, 2021).…”

Section: Beneficiosunclassified

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Trastornos hipertensivos durante el embarazo

Paneque¹,

Fernández²,

Quiñones³

et al. 2022

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La obra aborda aspectos importantes como: factores de riesgos, clasificación, algunas condiciones intrínsecas y extrínsecas vinculadas a esta patología, su etiopatogenia y fisiopatología, complicaciones maternas y perinatales; así como sus protocolos de atención, destacándose: el control de la hipertensión arterial, prevención de la convulsión eclámptica, vigilancia biológica y optimización de la extracción; con el propósito de estabilizar a la gestante en espera de la interrupción del embarazo como tratamiento definitivo que será dependiente de la edad gestacional y las condiciones clínicas materno fetales.

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“…GPCRs are the key factors for the occurrence and development of major diseases, including cardiometabolic diseases ( Dorsam and Gutkind, 2007 ; Lappano and Maggiolini, 2011 ; Wang et al, 2018 ). Exploratory studies have revealed the essential functions of GPCRs in placental development and provided a sufficient theoretical basis that they can be used as potential targets for PE ( Conrad, 2016 ; McGuane and Conrad, 2012 ; Quitterer and AbdAlla, 2021 ). Based on the classification by structure and phylogeny analysis of GPCRs, Class B GPCRs, which are structurally characterized by large extracellular regions, contain the following two families, secretin GPCRs and adhesion GPCRs.…”

Section: Introductionmentioning

confidence: 99%

Focusing on the role of secretin/adhesion (Class B) G protein-coupled receptors in placental development and preeclampsia

Yin

Guan

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Preeclampsia, a clinical syndrome mainly characterized by hypertension and proteinuria, with a worldwide incidence of 3–8% and high maternal mortality, is a risk factor highly associated with maternal and offspring cardiovascular disease. However, the etiology and pathogenesis of preeclampsia are complicated and have not been fully elucidated. Obesity, immunological diseases and endocrine metabolic diseases are high-risk factors for the development of preeclampsia. Effective methods to treat preeclampsia are lacking, and termination of pregnancy remains the only curative treatment for preeclampsia. The pathogenesis of preeclampsia include poor placentation, uteroplacental malperfusion, oxidative stress, endoplasmic reticulum stress, dysregulated immune tolerance, vascular inflammation and endothelial cell dysfunction. The notion that placenta is the core factor in the pathogenesis of preeclampsia is still prevailing. G protein-coupled receptors, the largest family of membrane proteins in eukaryotes and the largest drug target family to date, exhibit diversity in structure and function. Among them, the secretin/adhesion (Class B) G protein-coupled receptors are essential drug targets for human diseases, such as endocrine diseases and cardiometabolic diseases. Given the great value of the secretin/adhesion (Class B) G protein-coupled receptors in the regulation of cardiovascular system function and the drug target exploration, we summarize the role of these receptors in placental development and preeclampsia, and outlined the relevant pathological mechanisms, thereby providing potential drug targets for preeclampsia treatment.

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Pathological AT1R-B2R Protein Aggregation and Preeclampsia

Cited by 5 publications

References 144 publications

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

Angiotensin and Endothelin Receptor Structures With Implications for Signaling Regulation and Pharmacological Targeting

Trastornos hipertensivos durante el embarazo

Focusing on the role of secretin/adhesion (Class B) G protein-coupled receptors in placental development and preeclampsia

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