Adeno-associated viral vector-mediated hypoxia-regulated VEGF gene transfer promotes angiogenesis following focal cerebral ischemia in mice

Shen, Fanxia; Fan, Yuding; Su, Hua; Zhu, Yiqian; Chen, Yongmei; Liu, Weizhong; Young, William L.; Yang, Guo‐Yuan

doi:10.1038/sj.gt.3303048

Cited by 58 publications

(43 citation statements)

References 54 publications

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“…This complication has also been observed when VEGF-engineered myoblasts are implanted in the ischemic rat leg (42) and ischemic rat heart (30), indicating that the proper dose of VEGF is key to maintaining normal capillary phenotype. We use 2 ϫ 10 9 genome copies of AAV in this experiment because our previous experiment indicated that injection of 2 ϫ 10 9 genome copies of AAVVEGF can induce reproducible focal angiogenesis in the mature mouse brain, including the ischemic brain (16,38). In the AAVVEGFtransduced mice, the number of capillaries increased up to 133% and dilated capillaries up to 160%, and there were more visible dysplastic capillaries compared with those of the AAVlacZtransduced group.…”

Section: Discussionmentioning

confidence: 99%

Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation

Qin

Su²,

Marchuk³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussionmentioning

confidence: 99%

Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation

Qin

Su²,

Marchuk³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…We know that a reduced oxygen tension milieu may provide the stimulus required to promote VEGF production by BMSCs through the stimulation of hypoxia inducible factor expression. [39][40][41] We therefore propose that Netrin-1 may promote VEGF expression by BMSCs and other tissue cells in the hind limb. The reason may be because Netrin-1 promotes the survival rate of transplanted BMSCs in the ischaemic muscle, allowing them to generate more VEGF and differentiate into more ECs and SMCs, 42 which are then incorporated into vasculogenesis, angiogenesis and arteriogenesis.…”

Section: Discussionmentioning

confidence: 99%

Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia

Liu

Wang

et al. 2016

Diabetes and Vascular Disease Research

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This study examines the effect and mechanism of action of Netrin-1 on bone marrow mesenchymal stem cells in angiogenesis. Tube formation and migration of bone marrow mesenchymal stem cells were observed in cell culture. Bone marrow mesenchymal stem cells or Netrin-1-bone marrow mesenchymal stem cells were injected into the ischaemic area of the rat hind limb on the first day after surgery. Laser Doppler perfusion imaging was performed to analyse the levels of vascular endothelial growth factor in plasma and muscles, and immunohistochemistry and immunofluorescence were used to analyse angiogenesis. Bone marrow mesenchymal stem cells in medium containing Netrin-1 markedly increased the number of tubes formed and the migration of bone marrow mesenchymal stem cells compared with the untreated control group. The function of Netrin-1 in tube formation and migration is similar to vascular endothelial growth factor, and combined with vascular endothelial growth factor, Netrin-1 has more enhanced effect than in the other three groups. The Netrin-1-bone marrow mesenchymal stem cell group had better augmented blood-perfusion scores and vessel densities, as well as improved function of the ischaemic limb than that of the group injected with bone marrow mesenchymal stem cells (treated with bone marrow mesenchymal stem cells individually) or the control group (treated with medium). These results suggest that Netrin-1 has the ability to augment the angiogenesis of bone marrow mesenchymal stem cells and improve the function of the ischaemic hind limb by increasing the level of vascular endothelial growth factor.

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“…For the treatment of ischemic heart disease, angiogenic therapy is aimed at stimulating functional and sustainable new blood vessels. However, an excessively high-level expression of the angiogenic factor in vivo may result in side effects in nonischemic sites such as excessive angiogenesis, which will lead npg to adverse consequences in the retina, synovium, and other areas [12,33] . Thus, long-lasting and reasonably high levels of exogenous gene stimulation are needed for clinical success.…”

Section: Discussionmentioning

confidence: 99%

Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart

et al. 2011

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Aim: The aim of this study was to improve the delivery efficacy and target specificity of the pro-angiogenic gene CD151 to the ischemic heart. Methods: To achieve the inducible expression of adeno-associated viral (AAV)-delivered CD151 gene in only the ischemic myocardium, we generated an AAV construct in which CD151 expression can be controlled by the hypoxia response element (HRE) sequence from the human Enolase gene. The function of this vector was examined in rat H9C2 cardiac myoblasts and in ischemic rat myocardium. The expression of CD151 in the areas of ischemic myocardium was confirmed at the mRNA level by real-time PCR and on the protein level by Western blot, whereas the CD151 expression in the microvessels within the areas of ischemic myocardium was detected by immunohistochemistry. Results: HRE significantly enhances the expression of CD151 under hypoxic conditions or in the ischemic myocardium, and forced CD151 expression increases the number of microvessels in the ischemic myocardium. Conclusion: The AAV-mediated, HRE regulated delivery of the CD151 gene shows higher expression in the ischemic myocardium and more efficiently targets CD151 to the hypoxic regions after myocardial infarction.

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Adeno-associated viral vector-mediated hypoxia-regulated VEGF gene transfer promotes angiogenesis following focal cerebral ischemia in mice

Cited by 58 publications

References 54 publications

Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation

Increased tissue perfusion promotes capillary dysplasia in the ALK1-deficient mouse brain following VEGF stimulation

Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia

Adeno associated viral vector-delivered and hypoxia response element-regulated CD151 expression in ischemic rat heart

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