Tissue Factor: Factor Viia Complex Regulates The Angiogenic Factors In Extra Villous Trophoblast Cell Lines

Abstract

Background: Angiogenesis is crucial during placental development and function, and its dysregulation contributes different pathologies. Tissue Factor (TF) forms a complex with Factor VIIa (FVIIa), activating Protease-Activated Receptor 2 (PAR2), which influences pro-angiogenic responses. This study investigates TF: FVIIa-PAR2 signaling in HTR-8/SVneo cells, an in vitro model for villous trophoblast angiogenesis.

Methods: HTR-8/SVneo cells were treated with FVIIa and a PAR2 activating peptide (PAR2 AP), SLIGKV-NH2. Total RNA was extracted, reverse transcribed into complementary DNA (cDNA), and reverse transcriptase polymerase chain reaction (RT-PCR) was performed to assess gene expression of Vascular Endothelial Growth Factor (VEGF), Placenta Growth Factor (PGF), and Platelet-Derived Growth Factor (PDGF). Beta-actin (β-actin) served as the internal reference.

Results: FVIIa treatment significantly upregulated VEGF mRNA by approximately 0.1-fold (p<0.05), PGF mRNA by approximately 0.4-fold (p<0.05), and PDGF mRNA by approximately 0.4-fold (p<0.05) compared to untreated control. PAR2 AP similarly increased VEGF mRNA by approximately 0.1-fold (p>0.05), PGF mRNA by approximately 0.8-fold (p<0.01), and PDGF mRNA by approximately 0.9-fold (p<0.01) compared to control.

Conclusion: TF: FVIIa-PAR2 signaling potently upregulates key pro-angiogenic factors in HTR-8/SVneo cells, highlighting its critical role in placental angiogenesis and potential implications for pregnancy complications.