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The role of endoglin and its soluble form in pathogenesis of preeclampsia

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Abstract

Preeclampsia remains till today a leading cause of maternal and fetal morbidity and mortality. Pathophysiology of the disease is not yet fully elucidated, though it is evident that it revolves around placenta. Cellular ischemia in the preeclamptic placenta creates an imbalance between angiogenic and anti-angiogenic factors in maternal circulation. Endoglin, a transmembrane co-receptor of transforming growth factor β (TGF-β) demonstrating angiogenic effects, is involved in a variety of angiogenesis-dependent diseases with endothelial dysfunction, including preeclampsia. Endoglin expression is up-regulated in preeclamptic placentas, through mechanisms mainly induced by hypoxia, oxidative stress and oxysterol-mediated activation of liver X receptors. Overexpression of endoglin results in an increase of its soluble form in maternal circulation. Soluble endoglin represents the extracellular domain of membrane endoglin, cleaved by the action of metalloproteinases, predominantly matrix metalloproteinase-14. Released in circulation, soluble endoglin interferes in TGF-β1 and activin receptor-like kinase 1 signaling pathways and inhibits endothelial nitric oxide synthase activation, consequently deranging angiogenesis and promoting vasoconstriction. Due to these properties, soluble endoglin actively contributes to the impaired placentation observed in preeclampsia, as well as to the pathogenesis and manifestation of its clinical signs and symptoms, especially hypertension and proteinuria. The significant role of endoglin and soluble endoglin in pathophysiology of preeclampsia could have prognostic, diagnostic and therapeutic perspectives. Further research is essential to extensively explore the potential use of these molecules in the management of preeclampsia in clinical settings.

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Authors and Affiliations

  1. 2nd Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54624, Thessaloniki, Greece

    Georgia Margioula-Siarkou, Chrysoula Margioula-Siarkou, Stamatios Petousis, Eleftherios Vavoulidis, Konstantinos Dinas, Alexandros Sotiriadis & Georgios Mavromatidis

  2. 2nd Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Kosmas Margaritis

  3. Department of Obstetrics and Gynecology, IVF Unit, Villa Sofia Cervello Hospital, University of Palermo, Palermo, Italy

    Giuseppe Gullo

  4. Department of Radiology, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Maria Alexandratou

Authors
  1. Georgia Margioula-Siarkou
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  2. Chrysoula Margioula-Siarkou
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  3. Stamatios Petousis
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  4. Kosmas Margaritis
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  5. Eleftherios Vavoulidis
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  6. Giuseppe Gullo
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  7. Maria Alexandratou
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  8. Konstantinos Dinas
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  9. Alexandros Sotiriadis
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  10. Georgios Mavromatidis
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Contributions

All authors contributed to the conception and design of the work, the search of literature, the collection and analysis of data, the writing and revision of the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Georgia Margioula-Siarkou.

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Not applicable. The present article does not involve intervention on a population of humans and/or animals directly, it is a review of literature that gathers information from published articles.

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Not applicable. The present article does not involve intervention on a population of humans and/or animals directly, it is a review of literature that gathers information from published articles.

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Margioula-Siarkou, G., Margioula-Siarkou, C., Petousis, S. et al. The role of endoglin and its soluble form in pathogenesis of preeclampsia. Mol Cell Biochem 477, 479–491 (2022). https://doi.org/10.1007/s11010-021-04294-z

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  • DOI: https://doi.org/10.1007/s11010-021-04294-z

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