Cys-peptide mediates the protective role in preeclampsia-like rat and cell models.

OBJECTIVE: The present study was designed to investigate whether the novel peptide cysteine-based peptide (Cys-peptide) had protective effects on preeclamptic animal and cell models. METHODS: We investigated effects of Cys-peptide on (1) preeclamptic symptoms (e.g. hypertension, proteinuria, fetal growth restriction (FGR)) in preeclampia-like rat models induced by lipopolysaccharides (LPS), (2) TNFalpha-induced cytotoxicity of human umbilical vascular endothelial cells (HUVECs) and HTR-8 cells (an immortalised human trophoblast cell line), (3) endothelial dysfunction and injured angiogenesis, (4) migration and invasion of trophoblast cells induced by TNFalpha. RESULTS: Cys-peptide ameliorated LPS-induced hypertension, proteinuria and FGR and other PE symptoms in preeclampia-like rat models. In addition, Cys-peptide attenuated TNFalpha-induced cytotoxicity by decreasing soluble fms-like tyrosine kinase-1 (sFlt-1), endothelin-1 (ET-1) and tissue plasminogen activator (tPA) mRNA expression in both cells. Furthermore, Cys-peptide restored endothelial dysfunction and rescued angiogenesis caused by TNFalpha in vitro. Importantly, Cys-peptide could reverse insufficient ability to invade and migrate of trophoblast cells. CONCLUSIONS: These results suggest Cys-peptide can play beneficial roles in preeclampsia-like rat and cell models. Therefore, we propose that Cys-peptide is probably a novel therapeutic candidate for PE.