Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19

轻症或重症新冠肺炎女性胎盘内皮血栓形成和微血管损伤的分子机制研究

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作者:Arturo Flores-Pliego ,Jael Miranda ,Sara Vega-Torreblanca ,Yolotzin Valdespino-Vázquez ,Cecilia Helguera-Repetto ,Aurora Espejel-Nuñez ,Héctor Borboa-Olivares ,Salvador Espino Y Sosa ,Paloma Mateu-Rogell ,Moisés León-Juárez ,Victor Ramírez-Santes ,Arturo Cardona-Pérez ,Isabel Villegas-Mota ,Johnatan Torres-Torres ,Ángeles Juárez-Reyes ,Thelma Rizo-Pica ,Rosa O González ,Lorenza González-Mariscal ,Guadalupe Estrada-Gutierrez

Abstract

Clinical manifestations of coronavirus disease 2019 (COVID-19) in pregnant women are diverse, and little is known of the impact of the disease on placental physiology. Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been detected in the human placenta, and its binding receptor ACE2 is present in a variety of placental cells, including endothelium. Here, we analyze the impact of COVID-19 in placental endothelium, studying by immunofluorescence the expression of von Willebrand factor (vWf), claudin-5, and vascular endothelial (VE) cadherin in the decidua and chorionic villi of placentas from women with mild and severe COVID-19 in comparison to healthy controls. Our results indicate that: (1) vWf expression increases in the endothelium of decidua and chorionic villi of placentas derived from women with COVID-19, being higher in severe cases; (2) Claudin-5 and VE-cadherin expression decrease in the decidua and chorionic villus of placentas from women with severe COVID-19 but not in those with mild disease. Placental histological analysis reveals thrombosis, infarcts, and vascular wall remodeling, confirming the deleterious effect of COVID-19 on placental vessels. Together, these results suggest that placentas from women with COVID-19 have a condition of leaky endothelium and thrombosis, which is sensitive to disease severity.

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