Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration

Abstract

Cardiovascular disease is a leading cause of morbidity and mortality globally. Accumulating evidence indicates that local resident stem/progenitor cells play an important role in vascular regeneration. Recently, it is demonstrated that a histone deacetylase 7‐derived 7‐amino acid peptide (7A, MHSPGAD) is critical in modulating the mobilization and orientated differentiation of these stem/progenitor cells. Here, its therapeutic efficacy in vascular repair and regeneration is evaluated. In vitro functional analyses reveal that the 7A peptide, in particular phosphorylated 7A (7Ap, MH[pSer]PGAD), could increase stem cell antigen‐1 positive (Sca1+) vascular progenitor cell (VPC) migration and differentiation toward an endothelial cell lineage. Furthermore, local delivery of 7A as well as 7Ap could enhance angiogenesis and ameliorate vascular injury in ischaemic tissues; these findings are confirmed in a femoral artery injury model and a hindlimb ischaemia model, respectively. Importantly, sustained delivery of 7A, especially 7Ap, from tissue‐engineered vascular grafts could attract Sca1+‐VPC cells into the grafts, contributing to endothelialization and intima/media formation in the vascular graft. These results suggest that this novel type of peptides has great translational potential in vascular regenerative medicine.

Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction

“…Modification of synthetic grafts aims at promoting homing of progenitor cells by delivering chemotaxis factors or stem cell activators have been pursued as potential means to regenerate functional artery. [ 17,18 ] However, the critical roles of the immune cells widely playing roles in adult tissues repair, especially during biomaterial mediated regeneration, are scarcely considered.…”

A collagen hydrogel loaded with HDAC7-derived peptide promotes the regeneration of infarcted myocardium with functional improvement in a rodent model

“…Our research has shown that 7Ap treatment improved the capillary density and promoted neovascularization at the border zone of the ischemic heart. In a parallel study [12], we have demonstrated that the inclusion of 7A, especially the phosphorylated version, 7Ap, significantly increased endothelialization. The majority of the endothelial cells derived from the local resident Sca-1 + stem cells of the surrounding tissues, because 7Ap can serve as a chemoattractant for Sca-1 + stem cells and direct their differentiation toward the EC lineage.…”

“…The phosphorylated 7A (7Ap, MH[pSer]PGAD) was shown to increase stem cell migration, proliferation, and differentiation, especially that of vascular progenitor cells (VPCs). 7Ap enhanced angiogenesis, ameliorated vascular injury and promoted blood perfusion recovery in in a femoral artery injury model and a hindlimb ischaemia model [12]. According to the properties of 7Ap, in this study, we speculated that the peptide should greatly contribute to MI therapy.…”

A histone deacetylase 7-derived peptide promotes vascular regeneration via facilitating 14-3-3γ phosphorylation

“…Recently, we published some data on the role of 7A in EC differentiation and its contribution to tissue engineered vessel graft 21 and protection in cardiac fibrosis via hydrogel implication. 22 In this study, we focused on the demonstration of the translation of the 7A peptide and its function in signal transduction and vascular remodeling.…”