Conclusion and implication
Our data indicate that 11β-HSD2 is a crucial factor for placental development and maintaining balance release of pro- and anti-angiogenic factors in placenta. We reveal previously unrecognized role of placental 11β-HSD2 dysfunction in the pathogenesis of PE and immediately highlight innovative targets to counteract PE.
Keywords: preeclampsia; 11β-HSD2; glucocorticoids; ADAM17; placenta
Abbreviations:
11β-HSD, 11β-hydroxysteroid dehydrogenase; PE, preeclampsia; CBX, carbenoxolone; sFlt1, fms-like tyrosine kinase 1; PlGF, placental growth factor; ADAM, a disintegrin and metalloprotease; GC, glucocorticoids; IUGR, intrauterine growth retardation; ICG, indocyanine green; ICG-NPs, ICG-loaded nanoparticles; CSA, chondroitin sulfate A; ICG-CSA-NPs, ICG-NPs linked to CSA binding peptide; CBX-NPs, CBX-loaded nanoparticles; CBX-SCR, CBX-NPs linked to scramble peptide; CBX-CSA, CBX-NPs linked to CSA binding peptide; NAD, nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; EVT, extravillous cytotrophoblasts; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GD, gestational day; BP, blood pressure; VEGF, vascular endothelial growth factor; DEX, dexamethasone; MT, mesometrial triangle; GREs, glucocorticoid response elements; MMP, matrix metalloprotein; MAP, mean arterial pressure; TBC, trophoblast; SA, spiral artery.