Temporal and Spatial Regulation of Histone Deacetylase-7 and β-Catenin in Endothelial Cells

Hui, Sonya; Brunt, Keith R.; Husain, Mansoor

doi:10.1161/circresaha.110.219345

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…HDAC7 plays an important role in the maintenance of endothelium integrity . In a parallel study, we have demonstrated that mouse Hdac7 mRNA can undergo alternative translation to produce a biological active 7‐aa peptide, which functions as a phosphate transfer carrier in cellular signal transduction.…”

Section: Discussionmentioning

confidence: 86%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 86%

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

et al. 2018

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“…HDAC7 plays an important role in the maintenance of the cadherin-catenin complex (Hui, Brunt, & Husain, 2010;Margariti et al, 2010). It has been documented that PKD-mediated phosphorylation contributes to HDAC7 degradation leading to cell migration and proliferation (Sinnett-Smith et al, 2014;Wang et al, 2008).…”

Section: The Translation Shift Between 7aa-peptide and Hdac7 Proteinmentioning

confidence: 99%

214 A histone deacetylase 7-derived 7-amino acid peptide acts as a phosphorylation carrier

Yang

Moraga

et al. 2017

Heart

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compounds such as endothelin-1 (ET-1) and NO are required to maintain vascular tine. An imbalance, resulting in increased ET-1 and reduced NO levels promotes vascular stiffening and consequently diseases such as diabetic retinopathy, nephropathy and atherosclerosis. Diseases caused by an increased atherosclerosis burden including coronary heart disease and stroke are major causes of death in obese and diabetic populations. Aims Determine (1) whether enhanced Ab levels are sufficient to induce vascular dysfunction and (2) if reducing Ab production can reverse diet-induced vascular dysfunction. Methods Measurements of vascular function was determined in vivo by the vascular response to Acetylcholine (endothelial dependent or Sodium Nitroprusside (endothelial independent) using laser Doppler imaging in two studies; (i) Wild-type (C57BL/6) mice fed a regular chow diet were infused with murine ab42 or scrambled peptide (ScP; 3.36mg/kg) in aCSF for 6 weeks or (ii) a BACE1 inhibitor (M-3; 10mg/kg) or vehicle (DMSO/PBS) into diet-induced obese (DIO) C57BL/6 mice. Western blotting and ELISAs were used to measure vascular NO signalling and Ab production. Results Circulating levels of Ab42, not the more prevalent Ab40 isoform, are increased in both high fat fed mice and obese/diabetic human patients. Infusion of M-3 into DIO mice rescued endothelial dependent reactivity (M-3 27.1 ± 5.9, vehicle 1.3 ± 2.9; P<0.01). In contrast, infusion of Ab42 promoted impaired vascular responses Ab 14.1±3.7, ScP 38.3±3.2; P<0.001) on regular chow with no change in body weight. In line with our hypothesis infusion of Ab42 increases the ET-1/NO ratio (ScP 1.12b± 0.05, Ab42 5.35 ± 0.89; P<0.001), while DIO mice treated with a BACE1 inhibitor, thus with reduced plasma Ab42 levels, have a low ET-1/NO ratio (M-3 1.29 ± 0.9, DIO 4.6 ± 1.3; P<0.05). Conclusions We suggest that amyloid processing has a role in normal vascular function with aberrant processing leading to endothelial dysfunction and hypertension. Here we show that pharmacological inhibition of BACE1 can reverse diet-induced endothelial dysfunction, via modulation of plasma Ab42 levels, as infusion of Ab42 can promote the dysfunction independent of a high fat diet. Histone deacetylase 7 (HDAC7) belongs to the class II HDAC family and plays a pivotal role in the maintenance of endothelium integrity. There are 8 splicing variants in mouse HDAC7 mRNAs. Within the 5' terminal non-coding area of some variants, there exist some short open reading frames (sORFs). Whether these sORFs can be translated and whether the resulting peptides play roles in cellular physiology remain unclear. In this study, we demonstrated that one sORF encoding a 7-amino-acid (7-aa) peptide could be translated in vascular progenitor cells (VPCs). Importantly, this 7-aa peptide (7A) could transfer the phosphate group from the phosphorylated Ser393 site of MEKK1 to the Thr145 site of 14-3-3g protein.The phosphorylated 7A (7Ap) could then directly phosphorylate 14-3-3g protein in a cell-free, in-gel buffer system. The...

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Seasonal modulation of the testis transcriptome reveals insights into hibernation and reproductive adaptation in Onychostoma macrolepis

Ma,

Chen,

et al. 2024

Fish Physiol Biochem

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Temporal and Spatial Regulation of Histone Deacetylase-7 and β-Catenin in Endothelial Cells

Cited by 3 publications

References 32 publications

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

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

214 A histone deacetylase 7-derived 7-amino acid peptide acts as a phosphorylation carrier

Seasonal modulation of the testis transcriptome reveals insights into hibernation and reproductive adaptation in Onychostoma macrolepis

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