Growth factor-induced therapeutic neovascularization for ischaemic vascular disease: time for a re-evaluation?

Lekas, Michael; Lekas, Poli; Latter, David A.; Kutryk, Michael; Stewart, Duncan J.

doi:10.1097/01.hco.0000231409.69307.d2

Cited by 44 publications

(34 citation statements)

References 65 publications

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“…21,22 The spinotrapezius muscles are a pair of skeletal muscles located on the dorsum adjacent to either side of the spine and running between the fourth thoracic and third lumbar vertebrae in mice. The mouse spinotrapezius is well perfused with highly developed collateral vessels and arcade arteriole loops in C57Bl/6 mice, and is only 60-200 mm thick, thus allowing en face observation of the muscle tissue and microvascular networks.…”

Section: Fty720-induced Microvascular Remodelingmentioning

confidence: 99%

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Sefcik

Aronin

Awojoodu

et al. 2011

Tissue Engineering Part A

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Proper spatial and temporal regulation of microvascular remodeling is critical to the formation of functional vascular networks, spanning the various arterial, venous, capillary, and collateral vessel systems. Recently, our group has demonstrated that sustained release of sphingosine 1-phosphate (S1P) from biodegradable polymers promotes microvascular network growth and arteriolar expansion. In this study, we employed S1P receptorspecific compounds to activate and antagonize different combinations of S1P receptors to elucidate those receptors most critical for promotion of pharmacologically induced microvascular network growth. We show that S1P 1 and S1P 3 receptors act synergistically to enhance functional network formation via increased functional length density, arteriolar diameter expansion, and increased vascular branching in the dorsal skinfold window chamber model. FTY720, a potent activator of S1P 1 and S1P 3 , promoted a 107% and 153% increase in length density 3 and 7 days after implantation, respectively. It also increased arteriolar diameters by 60% and 85% 3 and 7 days after implantation. FTY720-stimulated branching in venules significantly more than unloaded poly(D, L-lactic-co-glycolic acid). When implanted on the mouse spinotrapezius muscle, FTY720 stimulated an arteriogenic response characterized by increased tortuosity and collateralization of branching microvascular networks. Our results demonstrate the effectiveness of S1P 1 and S1P 3 receptor-selective agonists (such as FTY720) in promoting microvascular growth for tissue engineering applications.

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Section: Fty720-induced Microvascular Remodelingmentioning

confidence: 99%

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Sefcik

Aronin

Awojoodu

et al. 2011

Tissue Engineering Part A

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“…However, clinical trials to date are negative or give conflicting results. [2][3][4] It is clear that collateral growth, angiogenesis, and vasculogenesis are parts of the same process in the succession of events leading to neovascularization, and it is likely that they may complement each other. Hence, to advance the therapeutic objective, strategies should focus on the promotion of neovascularization in general rather than targeting collateral growth or angiogenesis specifically.…”

mentioning

confidence: 99%

Inhibition of Prolyl Hydroxylase Domain Proteins Promotes Therapeutic Revascularization

et al. 2009

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Background-The hypoxia-inducible transcription factor (HIF) subunits are destabilized via the O 2 -dependent prolyl hydroxylase domain proteins (PHD1, PHD2, and PHD3). We investigated whether inhibition of PHDs via upregulating HIF might promote postischemic neovascularization. Methods and Results-Mice with right femoral artery ligation were treated, by in vivo electrotransfer, with plasmids encoding for an irrelevant short hairpin RNA (shRNA) (shCON [control]) or specific shRNAs directed against HIF-1␣ (shHIF-1␣), PHD1 (shPHD1), PHD2 (shPHD2), and PHD3 (shPHD3). The silencing of PHDs induced a specific and transient downregulation of their respective mRNA and protein levels at day 2 after ischemia and, as expected, upregulated HIF-1␣. As a consequence, 2 key hypoxia-inducible proangiogenic actors, vascular endothelial growth factor-A and endothelial nitric oxide synthase, were upregulated at the mRNA and protein levels. In addition, monocyte chemotactic protein-1 mRNA levels and infiltration of Mac-3-positive macrophages were enhanced in ischemic leg of mice treated with shPHD2 and shPHD3. Furthermore, activation of HIF-1␣-related pathways was associated with changes in postischemic neovascularization. At day 14, silencing of PHD2 and PHD3 increased vessel density by 2.2-and 2.6-fold, capillary density by 1.8-and 2.1-fold, and foot perfusion by 1.2-and 1.4-fold, respectively, compared with shCON (PϽ0.001). shPHD1 displayed a lower proangiogenic effect. Of interest, coadministration of shHIF-1␣ with shPHD3 abrogated shPHD3-related effects, suggesting that activation of endogenous HIF-1-dependent pathways mediated the proangiogenic effects of PHD silencing. Conclusions-We demonstrated that a direct inhibition of PHDs, and more particularly PHD3, promoted therapeutic revascularization. Furthermore, we showed that activation of the HIF-1 signaling pathway is required to promote this revascularization. (Circulation. 2009;120:50-59.)

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“…20 Therapeutic angiogenesis is proposed as a complement or an alternative to surgical revascularization. To date, several proangiogenic factors, including VEGF and fibroblast growth factor, have been tested and have demonstrated convincing efficiency in acute and chronic experimental models 21 ; however, clinical trials to test VEGF or fibroblast growth factor angiogenic therapy in coronary and peripheral artery diseases were disappointing because their effects were inconsistent. 21,22 One of the explanations for the lack of efficiency of angiogenic therapy probably comes from the use of individual factors, whereas angiogenesis is known to involve a plethora of angiogenic factors.…”

Section: Err-␥: a Potential Target For Ischemic Tissue Repairmentioning

confidence: 99%

Estrogen-Related Receptor-γ

Gadeau

Arnal

2012

Circulation Research

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Growth factor-induced therapeutic neovascularization for ischaemic vascular disease: time for a re-evaluation?

Cited by 44 publications

References 65 publications

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Selective Activation of Sphingosine 1-Phosphate Receptors 1 and 3 Promotes Local Microvascular Network Growth

Inhibition of Prolyl Hydroxylase Domain Proteins Promotes Therapeutic Revascularization

Estrogen-Related Receptor-γ

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