Altered AADAC Modulates Trophoblast Invasion and Suggests a Potential Angiogenic Regulatory Role in Severe Preeclampsia

TL;DR

This study explores how altered AADAC expression affects trophoblast invasion and angiogenesis in severe preeclampsia.

Contribution

The study identifies AADAC as a hypoxia-responsive gene influencing trophoblast function in preeclampsia.

Findings

AADAC expression is increased in preeclamptic placentas but reduced at the protein level.

Hypoxia increases AADAC and HIF-1α expression in trophoblast cells.

AADAC silencing enhances trophoblast invasion and tube formation under hypoxia.

Abstract

Preeclampsia (PE) is a serious pregnancy complication characterized by hypertension and organ dysfunction. Its pathogenesis involves impaired trophoblast invasion and inadequate spiral artery remodeling; however, the underlying molecular mechanisms remain unclear. This study investigated the role of arylacetamide deacetylase (AADAC) in PE and its effects on trophoblast function by analyzing placental tissues from 30 patients with PE and 15 controls. Exploratory RNA sequencing was performed on pooled placental samples from six patients with severe PE and six controls, and AADAC expression was validated by semi-quantitative PCR and Western blotting. HTR8/SVneo cells were exposed to cobalt chloride (CoCl2) under hypoxia-mimicking conditions, and AADAC expression was manipulated by siRNA-mediated knockdown (KD) and overexpression (OE). RNA sequencing revealed increased AADAC expression in PE placentas (fold change > 2.0, raw p < 0.05). Although AADAC mRNA levels were elevated in PE tissues, protein levels were reduced. CoCl2 exposure was associated with increased expression of AADAC and hypoxia-inducible factor-1 alpha (HIF-1α). Under hypoxia-mimicking conditions, AADAC silencing was associated with increased trophoblast invasion and tube formation, whereas AADAC overexpression reduced tube formation without significantly affecting invasion. These findings suggest that dysregulated, hypoxia-responsive AADAC expression influences trophoblast invasive and angiogenic behavior in preeclampsia.

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