P8RI peptide

P8RI(CD31 agonist), a retro-inverso sequence of the best candidate identified by functional in vitro screening of a peptide library, passed an absorption, distribution, metabolism, excretion and toxicology analysis. The IC50 of P8RI based on the human ether-a-go-go-related gene tail current amplitude was 150 μg/ml, which represents an ≈40-fold Cmax of the drug in the plasma of subcutaneously injected mice. Of note, at the concentration of 5 μg/ml, which is higher than the Cmax in the blood after subcutaneous injection, the peptide has no effect on the tail amplitude of the potassium channel. P8RI significantly affected the polarization of macrophages, resulting in a dramatic reduction in M1 markers such as the expression of iNOS and arginase II and the production of IL-6, IL-12p70, and TNF-α, whereas it enhanced the M2 phenotype, as detected by an increased expression of arginase I and production of IL-10. Curative treatment with P8RI promotes the healing of experimental dissecting aneurysm in atherosclerotic mice.