Peptides do not prevent cleavage of endoglin to produce soluble endoglin

• MMP14 cleaves endoglin at a specific peptide sequence to release soluble endoglin.
• Short peptides that carry this peptide sequence were administered and soluble endoglin measured.
• No effect on soluble endoglin was observed using JAR cells, primary explants, and primary HUVECs.
• No effect on soluble endoglin was observed using HEK293Ts overexpressing MMP14 and endoglin.
• Endoglin-like peptides do not inhibit soluble endoglin release.

MMP14 cleaves membrane bound endoglin to produce soluble endoglin (sEng), an anti-angiogenic factor that causes endothelial dysfunction in preeclampsia. A recent publication proposed peptides with an amino acid sequence straddling the MMP14 cleavage site on endoglin decreases sEng release. This may be an exciting therapeutic approach and requires validation. We administered peptides to JAR cells, and primary placental explants and endothelial cells. The peptides had no effect on sEng production, and did not block sEng production in HEK293 with MMP14 and endoglin overexpressed. Peptides with an amino acid sequence encompassing the cleavage site do not prevent sEng production in vitro.