A Novel Peptide Ameliorates TNF alpha- and LPS-Induced Endothelia Dysfunction in Preeclampsia

BACKGROUND To investigate the protective effects of the novel peptide antiendothelial dysfunction peptide in preeclampsia (AEDPPE) on tumor necrosis factor alpha (TNF alpha)- and lipopolysaccharide (LPS)-induced injury in the vascular endothelium in preeclampsia. METHODS The effects of AEDPPE on TNF alpha-induced vascular endothelial injury were assessed by enzyme-linked immunosorbent assay, quantitative real-time PCR, mitochondrial membrane potential assay, Cell Counting Kit-8 assay, THP-1 monocyte-human umbilical vein endothelial cell (HUVEC) adhesion assay, endothelial tube-forming assay, transcriptomic analysis, preeclamptic symptom analysis, and histological analysis in preeclampsia-like rat models induced by LPS. RESULTS AEDPPE alleviated the upregulation of antiangiogenic factors including soluble fms-like tyrosine kinase-1, endothelin-1, and tissue plasminogen activator and attenuated the reduction in mitochondrial potential induced by TNF alpha in HUVECs. In addition, AEDPPE treatment counteracted the decrease in tube formation and decreased the numbers of THP-1 monocytes attached to HUVECs caused by TNF alpha. Mechanistically, cytokine-cytokine receptor interactions enriched many genes and the TNF signaling pathway may be involved in this phenomenon. Moreover, cotreatment with LPS and AEDPPE significantly reversed the preeclampsia-like phenotype including hypertension and proteinuria and improved the functions of the kidney and placenta. CONCLUSIONS AEDPPE effectively ameliorated the vascular endothelial injury induced by TNF alpha and LPS in preeclampsia. We suggest that AEDPPE may be a novel therapeutic candidate for preeclampsia treatment. These findings demonstrate that AEDPPE may play an effective role in ameliorating vascular endothelial dysfunction and be a potential therapeutic agent for preeclampsia.