Comparative peptidomics analysis of preeclamptic placenta and the identification of a novel bioactive SERPINA1 C-terminal peptide

Preeclampsia (PE) is a life-threatening disease that severely harms pregnant women and infants' health but has a poorly understood etiology. Peptidomics can supply important information about the occurrence of diseases. However, application of peptidomics in preeclamptic placentas has never been reported. We conducted a comparative peptidomics analysis of PE placentas and performed bio-informatics analysis on differentially expressed peptides. Effects of differential peptide ⁴⁰⁵SPLFMGKVVNPTQK⁴¹⁸ on the behaviors of trophoblasts and angiogenesis were assessed by CCK8, transwell assays, and tube network formation assays. And we also confirmed the role of peptide in the zebrafish xenograft model. A total of 3582 peptide were identified. 48 peptides were differentially expressed. Bioinformatics analysis indicated that precursor proteins of these differentially expressed peptides correlate with "complement and coagulation cascades," and "platelet activation" pathways. Of the 48 differential peptides, we found that peptide ⁴⁰⁵SPLFMGKVVNPTQK⁴¹⁸ can significantly increase proliferation, migration of trophoblasts and stimulate angiogenesis of HUVECs in vitro and zebrafish model. These findings suggest peptidomes can aid in understanding the pathogenesis of PE more comprehensively. Peptide ⁴⁰⁵SPLFMGKVVNPTQK⁴¹⁸ can be novel target and strategy to alleviate the condition of preeclampsia.