Functional recovery of myocardial infarction by specific EBP-PR1P peptides bridging injectable cardiac extracellular matrix and vascular endothelial growth factor.

Abstract

Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor and plays an important role in therapy of myocardial infarction (MI). Currently, how to retain regional concentration and decrease rapid diffusion is critical for its clinical application of VEGF. In recent years, the application of targeting peptides has been developed rapidly and provides new strategies for the sustained release of VEGF. In present study, a bi-functional EBP-PR1P peptide was designed and bridged VEGF to injectable cardiac extracellular matrix (c-ECM). Through EBP-PR1P peptides, VEGF could specifically bind with c-ECM to realize the sustained release, without impacting the bioactivity of VEGF. Then VEGF/EBP-PR1P/c-ECM scaffolds were constructed and administrated into rats with MI. The results showed VEGF/EBP-PR1P/c-ECM could promote angiogenesis, protect cardiomyocytes survival against apoptosis, and improve the recovery of cardiac function. In addition, the mechanism of EBP-PR1P/VEGF was also investigated which canonical downstream of VEGF-Akt signaling pathway was activated. These results showed specific VEGF/EBP-PR1P/c-ECM scaffolds served as promising delivery system for VEGF that facilitated the functional recovery of MI.