Identification of novel peptide motifs in the serpin maspin that affect vascular smooth muscle cell function

Maspin is a non-inhibitory member of the serpin family that affects cell behaviours related to migration and survival.We have previously shown that peptides of the isolated G α-helix (G-helix) domain of maspin show bioactivity.Migration, invasion, adhesion and proliferation of vascular smooth muscle cells (VSMC) are important processes that contribute to the build-up of atherosclerotic plaques.Here we report the use of functional assays of these behaviours to investigate whether other maspin-derived peptides impact directly on VSMC; focusing on potential anti-atherogenic properties.We designed 18 new peptides from the structural moieties of maspin above ten amino acid residues in length and considered them beside the existing G-helix peptides.Of the novel peptides screened those with the sequences of maspin strand 4 and 5 of beta sheet B (S4B and S5B) reduced VSMC migration, invasion and proliferation, as well as increasing cell adhesion.A longer peptide combining these consecutive sequences showed a potentiation of responses, and a 7-mer contained all essential elements for functionality.This is the first time that these parts of maspin have been highlighted as having key roles affecting cell function.We present evidence for a mechanism whereby S4B and S5B act through ERK1/2 and AMP-activated protein kinase (AMPK) to influence VSMC responses.