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

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Histone Deacetylase 7‐Derived Peptides Play a Vital Role in Vascular Repair and Regeneration
Advanced Science ( IF 14.3 ) Pub Date : 2018-06-25 , DOI: 10.1002/advs.201800006
Yiwa Pan ₁ , Junyao Yang ₂ , Yongzhen Wei ₁ , He Wang ₁ , Rongkuan Jiao ₁ , Ana Moraga ₂ , Zhongyi Zhang ₂ , Yanhua Hu ₂ , Deling Kong ₁ , Qingbo Xu ₂ , Lingfang Zeng ₂ , Qiang Zhao _{1,

3}

Affiliation

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.

中文翻译：

组蛋白脱乙酰酶 7 衍生肽在血管修复和再生中发挥重要作用

心血管疾病是全球发病率和死亡率的主要原因。越来越多的证据表明，本地常驻干/祖细胞在血管再生中发挥着重要作用。最近，研究表明组蛋白脱乙酰酶 7 衍生的 7 个氨基酸肽（7A，MHSPGAD）对于调节这些干/祖细胞的动员和定向分化至关重要。在此，评估其在血管修复和再生方面的治疗效果。体外功能分析表明，7A 肽，特别是磷酸化 7A（7Ap，MH[pSer]PGAD），可以增加干细胞抗原 1 阳性 (Sca1 + )^血管祖细胞 (VPC) 向内皮细胞谱系的迁移和分化。此外，7A和7Ap的局部递送可以增强血管生成并改善缺血组织中的血管损伤。这些发现分别在股动脉损伤模型和后肢缺血模型中得到证实。重要的是，从组织工程血管移植物中持续输送 7A，尤其是 7Ap 可以将 Sca1 ⁺ ‐VPC 细胞吸引到移植物中，从而有助于血管移植物中的内皮化和内膜/中膜形成。这些结果表明这种新型肽在血管再生医学中具有巨大的转化潜力。

更新日期：2018-06-25

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