Ex vivo gene delivery of ephrin-B2 induces development of functional collateral vessels in a rabbit model of hind limb ischemia

Katsu, Masatake; Koyama, Hiroyuki; Maekawa, Hiromitsu; Kurihara, Hiroki; Uchida, Hiroaki; Hamada, Hirohumi

doi:10.1016/j.jvs.2008.08.007

Cited by 14 publications

(9 citation statements)

References 29 publications

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“…In the initial RTP, we included 127 genes that are known to be involved in neovascularization from both literature and our own studies (Online Table IA). As anticipated, we observed enrichment of putative binding sites for several microRNAs that were previously reported to influence postischemic neovascularization, including miR-17/92a 9 (29 and 21 putative target genes, respectively), miR-106b/93/25 8,14 (29,29, and 21 putative target genes, respectively), the miR-15a family 10,11,25 (26 putative target genes), miR-503 13 (11 putative target genes), and miR-100 7 (2 putative target genes) but not, for example, miR-126. 6 However, more outspoken was the enrichment of putative binding sites for 27 microRNAs from the 14q32 microRNA gene cluster, including miR-329, miR-494, and miR-495 (20, 31, and 44 putative target genes, respectively).…”

Section: Reverse Target Predictionsupporting

confidence: 83%

Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

Welten

Bastiaansen

Jong

et al. 2014

Circulation Research

135

161

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Rationale: Effective neovascularization is crucial for recovery after cardiovascular events. Objective: Because microRNAs regulate expression of up to several hundred target genes, we set out to identify microRNAs that target genes in all pathways of the multifactorial neovascularization process. Using www.targetscan. org, we performed a reverse target prediction analysis on a set of 197 genes involved in neovascularization. We found enrichment of binding sites for 27 microRNAs in a single microRNA gene cluster. Microarray analyses showed upregulation of 14q32 microRNAs during neovascularization in mice after single femoral artery ligation. Methods and Results:Gene silencing oligonucleotides (GSOs) were used to inhibit 4 14q32 microRNAs, miR-329, miR-487b, miR-494, and miR-495, 1 day before double femoral artery ligation. Blood flow recovery was followed by laser Doppler perfusion imaging. All 4 GSOs clearly improved blood flow recovery after ischemia. Mice treated with GSO-495 or GSO-329 showed increased perfusion already after 3 days (30% perfusion versus 15% in control), and those treated with GSO-329 showed a full recovery of perfusion after 7 days (versus 60% in control). Increased collateral artery diameters (arteriogenesis) were observed in adductor muscles of GSO-treated mice, as well as increased capillary densities (angiogenesis) in the ischemic soleus muscle. In vitro, treatment with GSOs led to increased sprout formation and increased arterial endothelial cell proliferation, as well as to increased arterial myofibroblast proliferation. Conclusions Welten et al 14q32 MicroRNAs in Neovascularization 697Both arteriogenesis and angiogenesis are highly multifactorial processes, and yet clinical trials aiming to induce neovascularization in patients with occlusive arterial disease have so far only focused on single-factor therapeutics, such as growth factors (eg, vascular endothelial growth factor A [VEGFA] and basic fibroblast growth factor [bFGF]). Unfortunately, these trials were less successful than anticipated.1,3,4 Growth factors only target 1 of multiple processes required for efficient neovascularization. Therefore, there is a need for novel proarteriogenic and proangiogenic factors that can act as master switches in neovascularization.MicroRNAs are endogenous RNA molecules that downregulate expression of their target genes.5 MicroRNAs do not completely silence their target genes, but rather downtune their expression. However, because each microRNA has multiple, up to several hundred, target genes, changes in microR-NA expression can have a major impact. Inhibition of a single microRNA can thus lead to activation of entire multifactorial physiological processes.Several studies have been published on the effects of microRNA inhibition on neovascularization, but in general, the focus of these studies lies with angiogenesis alone, not arteriogenesis. [6][7][8][9][10][11][12][13][14] In the present study, we exploited the master switch character of microRNAs to identify microRNAs that play a regulat...

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Section: Reverse Target Predictionsupporting

confidence: 83%

Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

Welten

Bastiaansen

Jong

et al. 2014

Circulation Research

135

161

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“…20 Several strategies have been developed to accelerate angiogenesis and thus overcome the strict diffusion limits imposed inside bioengineered tissues that are thicker than 500 mm. Such strategies include the provision of various proangiogenic factors, 21,22 genetic modification of cells to overproduce growth factors, 23,24 specific biomaterial design to mimic the extracellular matrix with high porosities, 25 and embedding ECs into engineered tissue constructs. 26,27 However, the time required for EC migration, angiogenic sprouting, and vasculogenesis is still too long to guarantee the viability of bioengineered tissue after implantation and for it to merge and fuse with host tissue.…”

Section: Discussionmentioning

confidence: 99%

Coculture of Stem Cells from Apical Papilla and Human Umbilical Vein Endothelial Cell Under Hypoxia Increases the Formation of Three-Dimensional Vessel-Like Structuresin Vitro

Yuan

Wang²,

Zhu

et al. 2015

Tissue Engineering Part A

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“…Likewise, conditions involving cyclic stretch and hypoxic stress can also increase Eph-B2 [127], whereas shear stress seems to decrease endothelial Eph-B2 expression [90]. Katsu et al [61] have also recently found that adenoviral delivery of Eph-B2 enhances collateral microvessel development in hindlimb ischemia (using a rabbit model), which even suggests a potential therapeutic role for Eph-B2. Based on these data, it would not be surprising to find the ephrins ligands and their receptor may play an important role in the regulation of skeletal muscle angiogenesis under physiologic conditions, and ⁄ or in response to exercise; however, at present evidence for this is still lacking.…”

Section: Other-derived Angiogenic Inhibitorsmentioning

confidence: 99%

Importance of Anti‐angiogenic Factors in the Regulation of Skeletal Muscle Angiogenesis

Olfert

Birot

2011

Microcirculation

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The microcirculation is essential for delivery of oxygen and nutrients to maintain skeletal muscle health and function. The network of microvessels surrounding skeletal myocytes has a remarkable plasticity that ensures a good match between muscle perfusion capacities and myofiber metabolic needs. Depending on physiologic conditions, this vascular plasticity can either involve growth (e.g., exercise-induced angiogenesis) or regression (e.g., physical deconditioning) of capillaries. This angio-adaptative response is thought to be controlled by a balance between pro- and anti-angiogenic factors and their receptors. While changes in the expression or activity for pro-angiogenic factors have been well studied in response to acute and chronic exercise during the past two decades, little attention thus far has been devoted to endogenous negative regulators that are also likely to be important in regulating capillary growth/regression. Indeed, the importance and contribution of anti-angiogenic factors in controlling skeletal muscle angiogenesis remains poorly understood. Here, we highlight the emerging research related to skeletal muscle expression of several negative angiogenic factors and discuss their potential importance in controlling skeletal muscle angio-adaptation, particularly in physiologic response to physical activity.

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Ex vivo gene delivery of ephrin-B2 induces development of functional collateral vessels in a rabbit model of hind limb ischemia

Cited by 14 publications

References 29 publications

Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

Coculture of Stem Cells from Apical Papilla and Human Umbilical Vein Endothelial Cell Under Hypoxia Increases the Formation of Three-Dimensional Vessel-Like Structuresin Vitro

Importance of Anti‐angiogenic Factors in the Regulation of Skeletal Muscle Angiogenesis

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