Gene therapy with the angiogenic cytokine secretoneurin induces therapeutic angiogenesis by a nitric oxide-dependent mechanism.

Circ Res 2009 Nov 1;105(10):994-1002. Epub 2009 Oct 1.

Department of Internal Medicine 1, Medical University of Innsbruck, Austria.

Rationale: The neuropeptide secretoneurin induces angiogenesis and postnatal vasculogenesis and is upregulated by hypoxia in skeletal muscle cells.

Objective: We sought to investigate the effects of secretoneurin on therapeutic angiogenesis.

Methods And Results: We generated a secretoneurin gene therapy vector. In the mouse hindlimb ischemia model secretoneurin gene therapy by intramuscular plasmid injection significantly increased secretoneurin content of injected muscles, improved functional parameters, reduced tissue necrosis, and restored blood perfusion. Increased muscular density of capillaries and arterioles/arteries demonstrates the capability of secretoneurin gene therapy to induce therapeutic angiogenesis and arteriogenesis. Furthermore, recruitment of endothelial progenitor cells was enhanced by secretoneurin gene therapy consistent with induction of postnatal vasculogenesis. Additionally, secretoneurin was able to activate nitric oxide synthase in endothelial cells and inhibition of nitric oxide inhibited secretoneurin-induced effects on chemotaxis and capillary tube formation in vitro. In vivo, secretoneurin induced nitric oxide production and inhibition of nitric oxide attenuated secretoneurin-induced effects on blood perfusion, angiogenesis, arteriogenesis, and vasculogenesis. Secretoneurin also induced upregulation of basic fibroblast growth factor and platelet-derived growth factor-B in endothelial cells.

Conclusions: In summary, our data indicate that gene therapy with secretoneurin induces therapeutic angiogenesis, arteriogenesis, and vasculogenesis in the hindlimb ischemia model by a nitric oxide-dependent mechanism.

Download full-text PDF

Source
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.109.19951
Publisher Site
http://dx.doi.org/10.1161/CIRCRESAHA.109.199513DOI Listing
November 2009
59 Reads

Publication Analysis

Top Keywords

gene therapy
24
nitric oxide
16
secretoneurin gene
16
secretoneurin induces
12
therapeutic angiogenesis
12
secretoneurin
12
angiogenesis arteriogenesis
12
postnatal vasculogenesis
8
blood perfusion
8
oxide-dependent mechanism
8
ischemia model
8
secretoneurin induced
8
inhibition nitric
8
secretoneurin-induced effects
8
hindlimb ischemia
8
nitric oxide-dependent
8
arteriogenesis vasculogenesis
8
induces therapeutic
8
nitric
6
gene
6

References

(Supplied by CrossRef)

J Cardiovasc Surg 1989

Similar Publications