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

Yongzhen Wei,Zhongyi Zhang,Ana Moraga,Lingfang Zeng,Yiwa Pan,Yanhua Hu,He Wang,Deling Kong,Qiang Zhao,Junyao Yang,Rongkuan Jiao,Qingbo Xu

doi:10.1002/advs.201800006

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.

Highlights

Introduction globallyAccumulating evidence indicates that local resident stem/progenitor cells play an important role in vascular regeneration
It is well documented that vascular progenitor cells (VPCs), which are of 7A, especially 7A peptide (7Ap), from tissue-engineered vascular grafts could attract mainly located in the adventitia, contribute
We demonstrated that a 7-amino acid-peptide (7A, MHSPGAD) could be alternatively translated from a short open reading frame within the 5′-terminal untranslated region of mouse Hdac7 mRNA in stem cell antigen-1 positive (Sca1+) VPCs in vitro

Summary

Cardiovascular disease is a leading cause of morbidity and mortality

Accumulating evidence indicates that local resident stem/progenitor cells play an important role in vascular regeneration It is Cardiovascular disease (CVD) represents a major cause of morbidity and mortality 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. Www.advancedsciencenews.com www.advancedscience.com phosphorylated by the activated kinase MEKK1 S393, which in turn could transfer the phosphate group to the Thr145 site of 14-3-3γ, forming a novel MEKK1-7A-14-3-3γ signaling pathway downstream of vascular endothelial growth factor (VEGF) This novel signaling pathway contributed to the activation of the Sca1+-VPCs.[16] In the present study, we focused on the functional analysis of this 7A peptide and its translational potential in vascular repair and regeneration by using different disease and transplantation models

Results

Discussion

Supporting Information

Conflict of Interest