Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia

Area of Science:

• Endocrinology
• Vascular Biology
• Genetics

Background:

• Preeclampsia is a pregnancy hypertensive disorder linked to endothelial dysfunction.
• The precise mechanisms driving endothelial dysfunction in preeclampsia are not fully understood.
• This research explores novel molecular pathways in endothelial cells (ECs) implicated in preeclampsia.

Purpose of the Study:

• To investigate potential novel mechanisms of endothelial cell (EC) dysfunction in preeclampsia.
• To identify and validate key genes involved in preeclampsia pathophysiology using transcriptional profiling and genetic analysis.

Main Methods:

• Human venous endothelial cells (ECs) were isolated from preeclamptic and normotensive postpartum individuals.
• Transcriptional profiling compared gene expression between groups.
• Vascular-specific Mendelian randomization and in vitro functional assays validated candidate genes.

Main Results:

• A significant association was found between higher genetically predicted METAP1 expression and increased preeclampsia risk.
• METAP1 overexpression in ECs reduced angiogenesis and cell proliferation.
• METAP1 influenced the expression of key preeclampsia-related genes, including VEGFA, FLT1, INHBA, and IL1B.

Conclusions:

• Elevated METAP1 expression in vascular endothelial cells (ECs) is causally linked to preeclampsia risk.
• METAP1 exhibits anti-angiogenic and pro-inflammatory effects in ECs, consistent with preeclampsia pathology.
• Ex vivo EC transcriptomics can uncover novel preeclampsia mechanisms, aiding in prevention and treatment strategies.