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Low-dose Aspirin Protective Effects Are Correlated With Deregulation of HNF Factor Expression in the Preeclamptic Placentas From Mice and Humans

Low-dose Aspirin Protective Effects Are Correlated With Deregulation of HNF Factor Expression in the Preeclamptic Placentas From Mice and Humans

Aurélien Ducat, Alexandra Vargas, Ludivine Doridot, Alessia Bagattin, Jonathan Lerner, Jean-Luc Vilotte, Christophe Buffat, Marco Pontoglio, Francisco Miralles, Daniel Vaiman

Cell Death Discov. 2019 May 10;5:94.

PMID: 31098302

Abstract:

Aspirin (acetyl-salicylic acid) is one of the most ancient drugs of the human pharmacopeia. Nonetheless, its action at low doses is not well understood at the molecular level. One of the applications of low-dose aspirin treatment is the prevention of preeclampsia (PE) in patients at risk. Foeto-placental overexpression of the STOX1A transcription factor in mice triggers PE symptoms. Transcriptomic analysis of the placentas, showed that aspirin massively down-regulates genes of the coagulation and complement cascade, as well as genes involved in lipid transport. The genes modified by aspirin treatment are not the ones that are modified by STOX1 overexpression, suggesting that aspirin could act downstream, symptomatically on the preeclamptic disease. Bioinformatics analysis of the promoters of the deregulated genes showed that they are strongly enriched in HNF transcription factors-binding sites, in accordance with existing literature showing their roles as regulators of coagulation. Two of these transcription factors, Hnf1β and Hnf4α are found down-regulated by aspirin treatment. In parallel, we show that in human patient placentas, aspirin-induced deregulations of genes of the coagulation cascade are also observed. Finally, the expression of Hnf1β target sequences (Kif12, F2, Hnf4α promoters and a synthetic concatemer of the Hnf1β-binding site) were investigated by transfection in trophoblast cell models, with or without aspirin treatment and with or without STOX1A overexpression. In this model we observed that STOX1A and aspirin tended to synergize in the down-regulation of Hnf1β target genes in trophoblasts.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP50782-B	Aspirin (Acetyl Salicylic Acid)		50-78-2	Price

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