VEGF loaded nanofiber membranes inhibit chronic cerebral hypoperfusion-induced cognitive dysfunction by promoting HIF-1a/VEGF mediated angiogenesis

Wu, Yuankui; Jin, Kai-Yan; Wang, Dapeng; Qi, Lin; Sun, Jun; Su, Shao-Hua; Hai, Jian

doi:10.1016/j.nano.2022.102639

Cited by 2 publications

(2 citation statements)

References 45 publications

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“…Given the diverse functions of HIF-1α in biological regulation mentioned above, activation of the HIF-1α signal pathway is promising in tissue repair, which allows the tissue to adapt to hypoxia and promptly re-establishes oxygen delivery to initiate the repair process . Recently, Wu et al designed VEGF-nanofiber membranes (NFM) to treat chronic cerebral hypoperfusion (CCH) rats and showed enhanced angiogenesis in the surgical temporal lobe cortex and hippocampus, suggesting that the HIF-1α/VEGF pathway could take part in angiogenesis . Thus, the HIF-1α/VEGF signaling pathway is expected to become a therapeutic target in lower limb ischemia, and the introduction of the HIF-1α gene can regulate cell proliferation and improve lower limb ischemia therapeutic outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…8 Recently, Wu et al designed VEGF-nanofiber membranes (NFM) to treat chronic cerebral hypoperfusion (CCH) rats and showed enhanced angiogenesis in the surgical temporal lobe cortex and hippocampus, suggesting that the HIF-1α/VEGF pathway could take part in angiogenesis. 9 Thus, the HIF-1α/VEGF signaling pathway is expected to become a therapeutic target in lower limb ischemia, and the introduction of the HIF-1α gene can regulate cell proliferation and improve lower limb ischemia therapeutic outcomes. However, the effects of endogenous upregulation of HIF-1α are limited due to its level and route of expression.…”

Section: Introductionmentioning

confidence: 99%

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Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment

Li,

Lu,

et al. 2024

ACS Appl. Bio Mater.

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Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxiainducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis. In this manuscript, effective gene delivery vector PEI-β-CD (PC) was reported for the first application in the hindlimb ischemia treatment to deliver HIF-1α plasmid in vitro and in vivo. Our in vitro finding demonstrated that PC/HIF-1α-pDNA could be successfully entered into the cells and mediated efficient gene transfection with good biocompatibility. More importantly, under hypoxic conditions, PC/HIF-1α-pDNA could up-regulate the HUEVC cell viability. In addition, the mRNA levels of VEGF, Ang-1, and PDGF were upregulated, and transcriptome results also demonstrated that the cell-related function of response to hypoxia was enhanced. The therapeutic effect of PC/HIF-1α-pDNA was further estimated in a murine acute hindlimb ischemia model, which demonstrated that intramuscular injection of PC/HIF-1α-pDNA resulted in significantly increased blood perfusion and alleviation in tissue damage, such as tissue fibrosis and inflammation. The results provide a rationale that HIF-1αmediated gene therapy might be a practical strategy for the treatment of limb ischemia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment

Li,

Lu,

et al. 2024

ACS Appl. Bio Mater.

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Liu,

Xie,

Zhou

et al. 2024

Neural Regeneration Research

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JOURNAL/nrgr/04.03/01300535-202502000-00028/figure1/v/2024-06-06T062529Z/r/image-tiff Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases. However, conventional topical drug delivery often results in a burst release of the drug, leading to transient retention (inefficacy) and undesirable diffusion (toxicity) in vivo. Therefore, a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke. Matrix metalloproteinase-2 (MMP-2) is gradually upregulated after cerebral ischemia. Herein, vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG (TIMP) and customizable peptide amphiphilic (PA) molecules to construct nanofiber hydrogel PA-TIMP-QK. PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro. The results indicated that PA-TIMP-QK promoted neuronal survival, restored local blood circulation, reduced blood-brain barrier permeability, and restored motor function. These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

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VEGF loaded nanofiber membranes inhibit chronic cerebral hypoperfusion-induced cognitive dysfunction by promoting HIF-1a/VEGF mediated angiogenesis

Cited by 2 publications

References 45 publications

Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment

Poly(ethylenimine)-Cyclodextrin-Based Cationic Polymer Mediated HIF-1α Gene Delivery for Hindlimb Ischemia Treatment

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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